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corresp

May 22, 2009

United States Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E., Mail Stop 3030

Washington, DC 20549

Attn: Russell Mancuso

    Re:

    Oculus Innovative Sciences, Inc.

Registration Statement on Form S-1

File No. 333-158539

Dear Mr. Mancuso:

I am securities counsel for Oculus Innovative Sciences, Inc. (the “Company”). I enclose for filing
under the Securities Act of 1933, as amended, Amendment No. 2 to the Form S-1, File No. 333-158539,
together with certain exhibits thereto (the “Registration Statement”).

The Registration Statement contains revisions that have been made in response to comments received
from the staff of the Securities and Exchange Commission (the “Staff”) in their letter dated April
27, 2009. Set forth below are the Company’s responses to the Staff’s comments. The numbering of
the responses corresponds to the numbering of the comments in the letter from the Staff.

Fee Table

    Comment 1.

    It appears from your prospectus that you intend to offer and
sell “Units” comprised of common stock and warrants.
Therefore, please include in your fee table the number of
“Units” you intend to offer and sell and calculate the
registration fee based on the fixed offering price of those
“Units.” Then include the appropriate fee calculation for
your offering of the warrants and shares underlying the units
and the shares underlying the warrants.

    Response 1.

    The Company has complied with the Staff’s comment.

Prospectus Cover

    Comment 2.

    Your disclosure on pages 18-19 indicates that the selling
stockholders will act independent of you with respect to the
securities they are offering for resale. The second paragraph
of your prospectus cover implies that the securities to be
offered and sold by them are part of your offering. Please
reconcile.

    Response 2.

    The Company has determined to no longer register the resale of
the securities held by the selling security holders. As such,
the Company has removed the disclosure related to the
secondary offering from the Registration Statement.

    Comment 3.

    If the selling stockholders are selling independent of your
fixed-price offering, please highlight that price difference
in your disclosure regarding the offering price on the
prospectus cover. Briefly explain the price difference in
your prospectus summary, and add appropriate risk factors.

    Response 3.

    The Company has determined to no longer register the resale of
the securities held by the selling security holders. As such,
the Company has removed the disclosure related to the
secondary offering from the Registration Statement.

    Comment 4.

    Please identify the placement agent for your offering here.
See Regulation S-K Item 501(b)(8).

    Response 4.

    The Company has complied with the Staff’s comment.

    Comment 5.

    Please ensure your cover page fully complies with Regulation
S-K Item 501(b)(4). For example, we note it appears that you
have not identified whether a market exists for the warrants
included in the Units.

    Response 5.

    The Company has complied with the Staff’s comment.

Selling Security Holders, page 16

    Comment 6.

    Your disclosure on pages 2 and 50 regarding the February 24,
2009 purchase agreement indicates that the investors in that
offering have not yet paid the full purchase price for the
securities. Generally, it is inconsistent with section 5 of
the Securities Act to register shares for resale before the
related private transaction is complete. Please provide us
with your analysis of how the private transaction was complete
at the time you filed this registration statement. Cite all
authority on which you rely.

    Response 6.

    The Company has determined to no longer register the resale of
the securities held by the selling security holders. As such,
the Company has removed the disclosure related to the
secondary offering from the Registration Statement.

    Comment 7.

    It appears from your notes to the selling security holders’
table that you are registering the resale of common stock
underlying Series C warrants. Given your disclosure in those
notes and on page 2 that the Series C warrants have not yet
been issued to you, it is premature to register the underlying
common stock for resale. Please revise or advise.

    Response 7.

    The Company has determined to no longer register the resale of
the securities held by the selling security holders. As such,
the Company has removed the disclosure related to the
secondary offering from the Registration Statement.

    Comment 8.

    Given the nature and size of the transaction you have
registered for the selling stockholders, including the shares
in the related registration statement file number 333-157776,
advise the staff of the Company’s basis for determining that
the transaction is appropriately characterized as a
transaction that is eligible to be made on a shelf basis under
Rule 415(a)(1)(i). We note, for example, that:

    –

    you have registered for resale by one of your directors and
parties related to him a significant number of shares relative to the amount
of shares outstanding and held by non-affiliates;

    –

    many of those shares cannot yet be acquired by your director
and related parties; and

    –

    the plans for a second tranche, the exercise period of the
warrants and your plans to issue replacements for exercised warrants appear to
result in a situation where you will be engaged in ongoing capital raising
from these investors while they may be obtaining funds from the public in this
offering.

    Response 8.

    The Company has determined to no longer register the resale of
the securities held by the selling security holders. As such,
the Company has removed the disclosure related to the
secondary offering from the Registration Statement.

    Comment 9.

    With a view toward disclosure, please tell use the market
price on the date of the purchase agreements with the selling
security holders compared to the per share price of the
securities you sold.

    Response 9.

    The Company has determined to no longer register the resale of
the securities held by the selling security holders. As such,
the Company has removed the disclosure related to the
secondary offering from the Registration Statement.

    Comment 10.

    Please provide us, with a view toward disclosure in the
prospectus, with tabular disclosure of the dollar amount of
each payment (including the value of any payments to be made
in common stock) in connection with the sale of the securities
that you have made or may be required to make to any selling
stockholder, any affiliate of a selling stockholder, or any
person with whom any selling stockholder has a contractual
relationship regarding the transaction (including any interest
payments, liquidated damages, payments made to “finders” or
“placement agents,” and any other payments or potential
payments). Please provide footnote disclosure of the terms of
each such payment.

    Further, please provide use, with a view toward disclosure in the prospectus, with
disclosure of the net proceeds to the issuer from the sale of the securities and
the total possible payments to all selling stockholders and any of their affiliates
in the first year following the sale of securities.

    Response 10.

    The Company has determined to no longer register the resale
of the securities held by the selling security holders. As
such, the Company has removed the disclosure related to the
secondary offering from the Registration Statement.

    Comment 11.

    Please provide us, with a view toward disclosure in the
prospectus, with tabular disclosure of the total possible
profit the selling stockholders could realize as a result of
any exercise of the warrants, presented in a table with the
following information disclosed separately:

    •

    the market price per share of the securities underlying the warrants on the
dates of the purchase agreement;

    •

    the exercise price per share of the underlying securities on the dates of
the purchase agreement, calculated as follows:

    –

    if the exercise price per share is set at a fixed
price, use the price per share established in the warrant; and

    –

    if the exercise price per share is not set at a fixed
price and, instead, is set at a floating rate in relationship to the
market price of the underlying security, determine the exercise price as
of the date of the purchase agreement;

    •

    the total possible shares underlying the warrants;

    •

    the combined market price of the total number of shares underlying the
warrants, calculated by using the market price per share on the dates of the
purchase agreement and the total possible shares underlying the warrants;

    •

    the total possible shares the selling shareholders may receive and the
combined exercise price of the total number of shares underlying the warrants
calculated by using the exercise price on the dates of the purchase agreement
and the total possible number of shares the selling stockholders may receive;
and

    •

    the total possible discount to the market price as of the dates of the
purchase agreement, calculated by subtracting the total exercise price on the
dates of the purchase agreement from the combined market price of the total
number of shares underlying the warrants on that date.

    If there are provisions in the warrants that could result in a change in the price
per share upon the occurrence of certain events, please provide additional tabular
disclosure as appropriate. For example, if the exercise price per share is fixed
unless and until the market price falls below a stated price, at which point the
exercise price per share drops to a lower price, please provide additional
disclosure.

    Response 11.

    The Company has determined to no longer register the resale
of the securities held by the selling security holders. As
such, the Company has removed the disclosure related to the
secondary offering from the Registration Statement.

    Comment 12.

    Please provide us, with a view toward disclosure in the
prospectus, with tabular disclosure of the total possible
profit to be realized as a result of any conversion/exercise
discounts for securities underlying any other warrants,
options, notes, or other securities of the issuer that are
held by the selling stockholders or any affiliates of the
selling stockholders, presented in a table with the following
information disclosed separately:

    •

    market price per share of the underlying securities on the date of the sale
of that other security;

    •

    the conversion/exercise price per share as of the date of the sale of that
other security, calculated as follows:

    –

    if the conversion/exercise price per share is set at
a fixed price, use the price per share on the date of the sale of that
other security; and

    –

    if the conversion/exercise price per share is not set
at a fixed price and, instead, is set at a floating rate in relationship
to the market price of the underlying security, use the
conversion/exercise discount rate and the market rate per share on the
date of the sale of that other security and determine the conversion price
per share as of that date;

    •

    the total possible shares to be received under the particular securities
(assuming complete conversion/exercise);

    •

    the combined market price of the total number of underlying shares,
calculated by using the market price per share on the date of the sale of that
other security and the total possible shares to be received;

    •

    the total possible shares to be received and the combined
conversion/exercise price of the total number of shares underlying that other
security calculated by using the conversion/exercise price on the date of the
sale of that other security and the total possible number of
underlying shares; and

    •

    the total possible discount to the market price as of the date of the sale
of that other security, calculated by subtracting the total
conversion/exercise price on the date of the sale of that other security from
the combined market price of the total number of underlying shares on that
date.

    Response 12.

    The Company has determined to no longer register the
resale of the securities held by the selling security
holders. As such, the Company has removed the
disclosure related to the secondary offering from the
Registration Statement.

    Comment 13.

    Please provide us, with a view toward disclosure in
the prospectus, with tabular disclosure of all prior
securities transactions between the issuer (or any of
its predecessors) and the selling stockholders, any
affiliates of the selling stockholders, or any person
with whom the selling stockholders has a contractual
relationship regarding the transaction (or any
predecessors of those persons), with the table
including the following information disclosed
separately for each transaction:

    •

    the date of the transaction;

    •

    the number of shares of the class of securities subject to the units
transactions that were outstanding prior to the transactions;

    •

    the number of shares of the class of securities subject to the transactions
that were outstanding prior to the transactions and held by persons other than
the selling stockholders, affiliates of the company, or affiliates of the
selling stockholders;

    •

    the number of shares of the class of securities subject to the transactions
that were issued or issuable in connection with the transactions;

    •

    the percentage of total issued and outstanding securities that were issued
or issuable in the transactions (assuming full issuance), with the percentage
calculated by taking the number of shares issued or issuable in connection
with the applicable transactions, and dividing that number by the number of
 shares issued and outstanding prior to the applicable transactions and held by
persons other than the selling stockholders, affiliates of the company, or
affiliates of the selling stockholders.

    •

    the market price per share of the class of securities subject to the
transactions immediately prior to the transactions (reverse split adjusted, if
necessary); and

    •

    the current market price per share of the class of securities subject to
the transaction (reverse split adjusted, if necessary).

    Response 13.

    The Company has determined to no longer register the resale
of the securities held by the selling security holders. As
such, the Company has removed the disclosure related to the
secondary offering from the Registration Statement.

    Comment 14.

    Please provide us, with a view toward disclosure in the
prospectus, with tabular disclosure comparing:

    •

    the number of shares outstanding prior to the date of the purchase
agreements that are held by persons other than the selling stockholders,
affiliates of the company, and affiliates of the selling stockholders;

    •

    the number of shares registered for resale by the selling stockholders or
affiliates of the selling stockholders in prior registration statements;

    •

    the number of shares registered for resale by the selling stockholders or
affiliates of the selling stockholder that continue to be held by the selling
stockholders or affiliates of the selling stockholders;

    •

    the number of shares that have been sold in registered resale transactions
by the selling stockholders or affiliates of the selling stockholders; and

    •

    the number of shares registered for resale on behalf of the selling
shareholders or affiliates of the selling stockholders in the current
transaction.

    In this analysis, the calculation of the number of outstanding shares should not
include any securities underlying any outstandi