Exhibit 32.1

Certifications

Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002

(Subsections (a) and (b) of Section 1350, Chapter 63 of Title 18, United States Code)

In connection with the Annual Report of Orexigen Therapeutics, Inc., a Delaware corporation (the Company), on
Form 10-K for the period ended December 31, 2010, as filed with the Securities and Exchange Commission on the date hereof (the Report), I, Michael A. Narachi, President and Chief Executive Officer of the Company, certify, pursuant
to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that to my knowledge:



| | 1. | The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and
| | -- | ---------------------------------------------------------------------------------------------------------------------



| | 2. | The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
| | -- | ----------------------------------------------------------------------------------------------------------------------------------------------------



|                      |  |                                                                                       |  |  |  | 
|--------------------- |  | ------------------------------------------------------------------------------------- |  |  |  | 
|Dated: March 11, 2011 |  | /s/    MICHAEL A.
NARACHI                                                            
|                      |  | Michael A. Narachi                                                                   
|                      |  | President and Chief Executive Officer
(principal executive officer of the registrant)

In connection with the Report, I, Graham K. Cooper, Chief Financial Officer and Treasurer of the Company, certify,
pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that to my knowledge:



| | 1. | The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and
| | -- | ---------------------------------------------------------------------------------------------------------------------



| | 2. | The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
| | -- | ----------------------------------------------------------------------------------------------------------------------------------------------------



|                      |  |                                                                                                      |  |  |  | 
|--------------------- |  | ---------------------------------------------------------------------------------------------------- |  |  |  | 
|Dated: March 11, 2011 |  | /s/    GRAHAM K.
COOPER                                                                             
|                      |  | Graham K. Cooper                                                                                    
|                      |  | Chief Financial Officer and Treasurer
(principal financial and accounting officer of the registrant)

The foregoing
certifications are being furnished solely to accompany the Report pursuant to 18 U.S.C. §1350, and are not being filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and are not to be incorporated by
reference into any filing of the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing. A signed original of this written statement required by Section 906 has been provided to
the Company and will be retained by the Company and furnished to the Securities and Exchange Commission or its staff upon request.