Background: Fluoxetine (FLX) is extensively used for the treatment of a diversity of psychiatric disorders, mainly depression. However,it can adversely affect male fertility. Aim of the Work This study was done to clarify the changes which take place in the testes after the oral administration of FLX and to evaluate the possible preventative role of curcumin. Materials and Methods Seventy-six adult male albino rats were randomly divided into four equal groups. Control group: kept without any treatment. Curcumin group: received daily dose of curcumin (150 mg/kg body weight) through oral gavage for 8 weeks. FLX group. They were given daily dose of FLX (10 mg/kg body weight) given through oral gavage for 8 weeks. FLX and curcumin group. They were given FLX together with curcumin with the same previous doses through oral gavage daily for 8 weeks. By the end of the experiment, blood samples were collected for the biochemical study of testosterone. All the animals were anaesthetized by ether inhalation, and the testis specimens were dissected out and weighed. The specimens were subjected to histopathological, immunohistochemical, and morphometrical evaluation. Results FLX decreased serum testosterone, diminished both epithelial height and diameter of seminiferous tubules, increased collagen fiber deposition in testicular tissue and induced positive immune reaction to B-cell lymphoma-2-associated X protein. In the FLX and curcumin group, the FLX-induced changes were less remarkable. Conclusion Exposure to FLX led to pronounced testicular alterations. Co-administration of curcumin with FLX ameliorated these changes.