United States securities and exchange commission logo January 6, 2022 Michael Grey Interim Chief Executive Officer Spruce Biosciences, Inc. 2001 Junipero Serra Boulevard, Suite 640 Daly City, California 94014 Re: Spruce Biosciences, Inc. Registration Statement on Form S-3 Filed December 30, 2021 File No. 333-261960 Dear Mr. Grey: This is to advise you that we have not reviewed and will not review your registration statement. Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you that the company and its management are responsible for the accuracy and adequacy of their disclosures, notwithstanding any review, comments, action or absence of action by the staff. Please contact Chris Edwards at 202-551-6761 with any questions. Sincerely, Division of Corporation Finance Office of Life Sciences cc: Daniel P. Eitutis