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                              March 29, 2024

       Lonnel Coats
       Chief Executive Officer
       Lexicon Pharmaceuticals, Inc.
       2445 Technology Forest Blvd., 11th Floor
       The Woodlands, TX 77381

                                                        Re: Lexicon 
Pharmaceuticals, Inc.
                                                            Registration 
Statement on Form S-3
                                                            Filed March 25, 
2024
                                                            File No. 333-278210

       Dear Lonnel Coats:

              We have conducted a limited review of your registration statement 
and have the
       following comment.

              Please respond to this letter by amending your registration 
statement and providing the
       requested information. If you do not believe a comment applies to your 
facts and circumstances
       or do not believe an amendment is appropriate, please tell us why in 
your response.

              After reviewing any amendment to your registration statement and 
the information you
       provide in response to this letter, we may have additional comments.

       Registration Statement on Form S-3

       General

   1.                                                   We note that you are 
registering the resale of up to 57,661,250 shares of common
                                                        stock. However, we note 
from your disclosure on page 12 that you currently have
                                                        300,000,000 shares of 
common stock authorized at this time. Please either revise the
                                                        resale offering so that 
the volume of common stock registered in the resale offering does
                                                        not exceed the number 
of shares of common stock that remain available for issuance at the
                                                        time you anticipate 
having the registration statement declared effective or revise to update
                                                        your disclosure and 
opinion of counsel once the amendment to your charter referenced on
                                                        page 5 has been 
approved by your stockholders. For guidance, refer to Section
                                                        II.B.1.a of Staff Legal 
Bulletin No. 19.

              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
 Lonnel Coats
Lexicon Pharmaceuticals, Inc.
March 29, 2024
Page 2

action by the staff.

       Refer to Rules 460 and 461 regarding requests for acceleration. Please 
allow adequate
time for us to review any amendment prior to the requested effective date of 
the registration
statement.

       Please contact Tyler Howes at 202-551-3370 or Tim Buchmiller at 
202-551-3635 with
any other questions.



                                                           Sincerely,
FirstName LastNameLonnel Coats
                                                           Division of 
Corporation Finance
Comapany NameLexicon Pharmaceuticals, Inc.
                                                           Office of Life 
Sciences
March 29, 2024 Page 2
cc:       Jackson A. O'Maley, Esq.
FirstName LastName