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    1320 Centre Street, Suite 202

Newton, MA 02459

Phone: 617-243-0060

Fax: 617-243-0066

June 18, 2009

United States Securities and Exchange Commission

Division of Corporation Finance

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

Washington, DC 20549

Attn: Geoffrey Kruczek

    Re:

    Oculus Innovative Sciences, Inc.

Registration Statement on Form S-1

File No. 333-158539

Dear Mr. Kruczek:

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 June
3, 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.

    Comment 1.

    We note your response to prior comment 8; however, it
continues to appear that you have registered for resale in
other registration statements securities held in the name of
one of your directors and affiliates that raise the issues
mentioned in that comment. Therefore, we reissue the comment.

    Response 1.

    On March 9, 2009, the Company filed a registration statement on Form S-1 (the “March
Registration Statement”). The Staff declared the March Registration Statement effective on March
26, 2009. The March Registration Statement registered shares from two transactions.

On February 6, 2009, the Company entered into Purchase Agreements with a group of accredited
investors whereby the Company raised $1,752,803 in gross proceeds through a private placement of
1,499,404 units.

For each $116.90 invested, an investor received:

    •
    One hundred shares of common stock, par value $0.0001 per share;

    •
    A Series A Warrant to purchase fifty-eight shares of common stock at
an exercise price of $1.87 per share. The Series A Warrants are
exercisable after six months and have a five year term;

    •
    A Series B Warrant to purchase seventy-eight shares of common stock at
an exercise price of $1.13 per share. The Series B Warrants are
exercisable after six months and have a three year term; and

    •
    For every two shares of common stock the investor purchases upon
exercise of a Series B Warrant, the investor will receive an
additional Series C Warrant to purchase one share of common stock. The
Series C Warrants are exercisable after six months and will have
an exercise price of $1.94 and a five year term.

The Company issued an aggregate of 1,499,404 shares of common stock, Series A Warrants to purchase
869,658 shares of its common stock and Series B Warrants to purchase 1,169,544 shares of its common
stock. As of the date of this letter, the Company has not issued any Series C Warrants because no
Series B Warrants have been exercised. As compensation for services rendered as the exclusive
placement agent for the offering, Merriman Curhan Ford & Co. received $122,696 in cash plus
warrants, exercisable upon the closing date of the transaction for a five year term, to purchase
104,958 shares of common stock at an exercise price of $1.56 per share.

On February 24, 2009, the Company entered into a Purchase Agreement with Robert Burlingame, a
Director, and Seamus Burlingame, an accredited investor unaffiliated with the Company. Pursuant to
the terms of the Purchase Agreement, the investors agreed to make a
$3,000,000 investment in the
Company. The investors paid $1,000,000 on February 24, 2009 and agreed to pay $2,000,000 no later
than August 1, 2009. In exchange for this investment, the Company agreed to issue to the investors
a total of 2,564,103 shares of common stock in two tranches, pro rata to the investment amounts
paid by the investor on each date the investors provide funds.

In addition, the Company agreed to issue to the investors Series A Warrants to purchase a total of
1,500,000 shares of common stock pro rata to the number of shares of common stock issued on each
Closing Date at an exercise price of $1.87 per share. The Series A Warrants will be exercisable
after six months and will have a five year term. The Company also agreed to issue to the
investors Series B Warrants to purchase a total of 2,000,000 shares of common stock pro rata to the
number of shares of common stock issued on each closing date at an exercise price of $1.13 per
share. The Series B Warrants will be exercisable after six months and will have a three year term.
In addition, for every two shares of common stock the investor purchases upon exercise of a Series
B Warrant, the investor will receive an additional Series C Warrant to purchase one share of common
stock. The Series C Warrant will be exercisable after six months and will have an exercise price
of $1.94 per share and a five year term. The Company will only be obligated to issue Series C Warrants to
purchase up to 1,000,000 shares of common stock. As of the date of this letter, the Company has
not issued any Series C Warrants because no Series B Warrants have been exercised.

The
investors in the financings (the “Investors”) were all accredited investors. Additionally, all of the Investors
were unaffiliated with the Company except for Robert Burlingame, who currently serves as a Director
of the Company. The 218,234 shares registered for Robert Burlingame in the March Registration
Statement represent less than 5% of the shares registered on the March Registration Statement and
approximately 1% of the shares outstanding at the time the March Registration Statement was
declared effective by the Staff. According to the March Registration Statement, the Company had
18,402,820 shares of common stock outstanding on March 18, 2009. At the time of effectiveness, the
March Registration Statement registered 4,886,724 shares or 26.6% of the total number of shares
outstanding. The amount of shares registered, however, includes 2,512,612 shares underlying warrants. If the warrants were exercised, the shares registered in the March Registration Statement
would be 23.4% of the total number of shares outstanding.

The securities issued in the financings were issued pursuant to the exemption from registration
provided by Section 4(2) of the Securities Act of 1933, as amended (the “Act”) and Regulation D
promulgated thereunder. The Investors made extensive representations and warranties regarding
their investment intent, including representations that they were purchasing their securities for
their own accounts, for investment purposes and not for the purpose of effecting any distribution
of the securities in violation of the Act.

The terms
of the financings do not include any price “re-sets,” floating price conversion rights or
other “toxic” features that have prompted the Staff’s concerns regarding “Extreme Convertible”
transactions.

Rule 415 Analysis

In 1983, the Commission adopted Rule 415 under the Act to permit the registration of offerings to be
made on a delayed or continuous basis. Rule 415 specifies certain

conditions that must be met by an issuer in order to avail itself of the Rule. In relevant part,
Rule 415 provides:

     “(a) Securities may be registered for an offering to be made on a continuous
or delayed basis in the future, Provided, That:

(1) The registration statement pertains only to:

(i) Securities which are to be offered or sold solely by or on behalf of a
person or persons other than the registrant, a subsidiary of the registrant or a
person of which the registrant is a subsidiary;...[or]

(x) Securities registered (or qualified to be registered) on Form S–3 or Form
F–3 (§239.13 or §239.33 of this chapter) which are to be offered and sold on an
immediate, continuous or delayed basis by or on behalf of the registrant, a
majority-owned subsidiary of the registrant or a person of which the registrant is
a majority-owned subsidiary....”

Under Rule 415(a)(1)(i), an issuer may register shares to be sold on a delayed or continuous basis
by selling stockholders in a bona fide secondary offering without restriction.

In the event that an offering registered in reliance on Rule 415(a)(1)(i) is deemed to be an
offering that is “by or on behalf of the registrant” as specified in Rule 415(a)(1)(x), Rule 415
contains additional limitations. Rule 415(a)(4) provides that

“In the case of a registration statement pertaining to an at the market offering
of equity securities by or on behalf of the registrant, the offering must come
within paragraph (a)(1)(x) of this section. As used in this paragraph, the term
‘at the market offering’ means an offering of equity securities into an existing
trading market for outstanding shares of the same class at other than a fixed
price.”

As a result, if an offering that purports to be a secondary offering is characterized as an
offering “by or on behalf of the registrant,” Rule 415 is only available to register an “at the
market offering” if the registrant is eligible to use Form S-3 or Form F-3 to register a primary
offering. The Company is not eligible to use Form S-3 to effect a primary offering. As a result,
it cannot use Rule 415 to register a primary offering “at the market.”

In the event that the offering registered by the Registration Statement is recharacterized as a
primary offering on behalf of the Company, (i) the offering would have to be made on a fixed price
basis (in other words, the Investors would not be able to sell their securities at prevailing
market prices), (ii) the Investors would be deemed to be “underwriters” with respect to the
financings (with the associated liabilities under Section 11 of the Act) and (iii) in accordance with
the Staff’s long-standing interpretive position, Rule 144 would never be available to them to
effect resales of their securities.

The
Staff’s interpretation of Rule 415 has a potentially disastrous impact on the
ability of a selling shareholder to effect the resale of its
securities. Because such a mischaracterization can have a chilling
effect on the ability of smaller public companies — like the Company — to raise capital, the
Staff should only recharacterize a secondary offering as being on behalf of a registrant after
careful and complete review of the relevant facts and circumstances.

The Staff has previously recognized the delicacy with which the analysis of a particular
transaction must be undertaken. In its Manual of Publicly Available Telephone Interpretations (the
“Telephone Interpretations Manual”), the Staff has set forth a detailed analysis of the relevant
factors that should be examined. Interpretation D.29 (the “Interpretation”) provides that:

“It is important to identify whether a purported secondary offering is really a
primary offering, i.e., the selling shareholders are actually underwriters selling
on behalf of an issuer. Underwriter status may involve additional disclosure,
including an acknowledgment of the seller’s prospectus delivery requirements. In
an offering involving Rule 415 or Form S-3, if the offering is deemed to be on
behalf of the issuer, the Rule and Form in some cases will be unavailable (e.g.,
because of the Form S-3 ‘public float’ test for a primary offering, or because
Rule 415 (a)(1)(i) is available for secondary offerings, but primary offerings
must meet the requirements of one of the other subsections of Rule 415). The
question of whether an offering styled a secondary one is really on behalf of the
issuer is a difficult factual one, not merely a question of who receives
the proceeds. Consideration should be given to how long the selling
shareholders have held the shares, the circumstances under which they received
them, their relationship to the issuer, the amount of shares involved, whether the
sellers are in the business of underwriting securities, and finally, whether under
all the circumstances it appears that the seller is acting as a conduit for the
issuer.” (emphasis added)

As the Interpretation indicates, the question is a “difficult” and “factual” one that involves an
analysis of many factors and “all the circumstances.”

Each of the relevant factors listed in the Interpretation is discussed below in the context of the
financings.

How Long the Selling Shareholders Have Held the Shares

Presumably, the longer shares are held, the less likely it is that the selling shareholders are
acting as a mere conduit for the Company. All of the warrants issued in the financings had a six
month delay before they could be exercised. Six months have not elapsed since the warrants were
issued and therefore none of the shares registered in the March Registration Statement that could
be issued upon exercise of the warrants have been sold. Additionally, the Company can confirm that
Robert Burlingame continues to hold the shares he was issued in the February 2009 financing. Given
that the March Registration Statement has been declared effective by the Staff, the Company is not
aware of whether the non-affiliate investors continue to hold their shares of common stock.

In the March 1999 Supplement to the Telephone Interpretations Manual, the Staff codified its
“PIPEs” interpretation. Interpretation 3S (the “PIPEs Interpretation”) provides in relevant part
that:

“In a PIPE transaction (private-investment, public-equity), the staff will not
object if a company registers the resale of securities prior to their issuance if
the company has completed a Section 4(2)-exempt sale of the securities (or in the
case of convertible securities, of the convertible security itself) to the
investor, and the investor is at market risk at the time of filing of the resale
registration statement....The closing of the private placement of the unissued
securities must occur within a short time after the effectiveness of the resale
registration statement.”

The PIPEs Interpretation contemplates that a valid secondary offering could occur
immediately following the closing of the placement. Since no holding period is required
for a PIPE transaction to be a valid secondary offering, by definition a holding period of nearly
one year must also be sufficient for a valid secondary offering.

This concept comports with longstanding custom and practice in the PIPEs marketplace. It is very
common in PIPE transactions — including this one – for the company to file a registration
statement shortly after closing (typically 30 days) and declared effective shortly thereafter
(typically 90 to 120 days after closing). Many of these transactions have been reviewed by the Staff and
the Staff, to my knowledge, has not indicated that the period of time elapsing between closing and
registration raised concerns about whether the offering is a valid secondary offering. Such concerns would be inconsistent with the PIPEs Interpretation.

The Circumstances Under Which They Received the Shares

As
described above, the securities covered by the March Registration
Statement were issued in a valid
private placement that complied in all respects with the PIPEs Interpretation, Section 4(2) of the
Act and Regulation D promulgated thereunder. As noted above, the terms of the Warrants contain no “toxic” provisions or other

terms that merited any special concerns by the Staff. All of the Investors purchased their
securities for investment and specifically represented that they were not acquiring their
securities with the purpose or intent of effecting a distribution in violation of the Act. There
is no evidence to suggest that those representations are false.

The Staff has appeared to take the position that
 registration indicates an intent to distribute.
However, this perspective is flawed and is at odds with both market practices and the
Staff’s own previous interpretive positions, including the