Filed Pursuant to Rule 424(b)(3)

Registration No. 333-264686

Prospectus Supplement No. 7

(To Prospectus dated June 24, 2022)

Comera Life Sciences Holdings, Inc.

1,946,846 Warrants to Purchase Common Stock

15,093,712 Shares of Common Stock Including

1,946,846 Shares of Common Stock issuable upon the

exercise of Warrants and 342,755 Shares of Common Stock

issuable upon conversion of the

Series A Convertible Perpetual

Preferred Stock

offered by Selling Securityholders

This prospectus supplement no. 7 (this “Prospectus Supplement”) updates, amends and supplements the prospectus dated June 24, 2022 (as amended or supplemented from time to time, the “Prospectus”) which forms a part of the Registration Statement on Form S-1 (Registration Statement No. 333-264686) filed by Comera Life Sciences Holdings, Inc. (“Holdco”). Capitalized terms used in this Prospectus Supplement and not otherwise defined herein have the meanings specified in the Prospectus.

This Prospectus Supplement is being filed to update, amend and supplement the information included or incorporated by reference in the Prospectus with the information contained in our Current Report on Form 8-K, filed with the Securities and Exchange Commission (the “SEC”) on February 21, 2023 (the “Current Report”). Accordingly, we have attached the Current Report to this Prospectus Supplement.

This Prospectus Supplement is not complete without, and may not be delivered or utilized except in combination with, the Prospectus, including any amendments or supplements thereto. This Prospectus Supplement should be read in conjunction with the Prospectus and any amendments or supplements thereto. If there is any inconsistency between the information in the Prospectus and this Prospectus Supplement, you should rely on the information in this Prospectus Supplement.

The Holdco Common Stock is listed on The Nasdaq Capital Market (“Nasdaq”) under the symbol “CMRA” and the Holdco Warrants are listed on Nasdaq under the symbol “CMRAW”. On February 17, 2023, the closing sale price of the Holdco Common Stock as reported on Nasdaq was $1.285 per share, and the closing sale price of the Holdco Warrants as reported on Nasdaq was $0.065 per warrant.

Investing in our securities involves a high degree of risk. Before buying any securities, you should carefully read the discussion of the risks of investing in our securities in “Risk Factors” beginning on page 14 of the Prospectus.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of the securities to be issued under the Prospectus or passed upon the accuracy or adequacy of the Prospectus. Any representation to the contrary is a criminal offense.

The date of this Prospectus Supplement is February 21, 2023.

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): February 14, 2023

Comera Life Sciences Holdings, Inc.

(Exact name of registrant as specified in its charter)

Registrant’s telephone number, including area code: (617) 871-2101

Not Applicable

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

Securities registered pursuant to Section 12(b) of the Act:

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

On February 14, 2023, the Board of Directors (the “Board”) of Comera Life Sciences Holdings, Inc. (the “Company”) met to determine the non-equity incentive compensation to be paid to each of Jeffrey Hackman, the Company’s Chairman, President and Chief Executive Officer, Michael Campbell, the Company’s Chief Financial Officer and Neal Muni, the Company’s Chief Operating Officer (together the “Named Executive Officers”) in respect of their achievement of 2022 performance objectives. In furtherance of the Company’s cash conservation efforts and to better align the interests of the Named Executive Officers with those of the Company’s stockholders, the Board elected to grant options (the “Options”) to purchase shares of the Company’s common stock, $0.0001 par value per share (the “Common Stock”) to the Named Executive Officers in lieu of performance-based cash compensation. The Options were granted under the Comera Life Sciences Holdings, Inc. 2022 Equity and Incentive Plan (the “2022 Plan”) and have an exercise price of $1.30 per share, the closing price of the Common Stock on the date of grant. Twenty-five percent of the shares underlying the Options vest on February 14, 2024, with the remaining shares vesting on a monthly basis on the 14^th day of each month thereafter, in each case, subject to continuous service to the Company, such that the Options shall be fully vested on February 14, 2027.

The Company filed a Registration Statement on Form S-1 with the Securities and Exchange Commission (the “SEC”) on February 3, 2023, as amended on February 8, 2023, which was declared effective on February 10, 2023 (File No. 333-269564) (the “Registration Statement”). The Summary Compensation Table included in the Registration Statement did not include non-equity incentive plan compensation paid to the Named Executive Officers for fiscal 2022 because 2022 non-equity incentive plan compensation had not yet been determined. In accordance with Item 5.02(f) of Form 8-K, the table below is updated to provide this information.

SUMMARY COMPENSATION TABLE

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.