Abstract17α-ethynilestradiol (EE₂) and tamoxifen (Tmx) are pollutants world-wide distributed in aquatic environments. Gilthead seabream, Sparus aurata L., is highlighted as a species model of intensively culture in anthropogenic disturbed environments. The effects of these pollutants on gilthead seabream reproduction and some immune responses have been described but, the humoral innate antimicrobial activities have never received attention. In this work we analysed the latest in the plasma of gilthead seabream males of different ages and reproductive stages treated with 0, 2.5, 5 or 50 μg EE₂ or 100 μg Tmx g⁻¹ food during different times of exposure and of reverting to commercial diet (recovery). The peroxidase and protease activities decreased as the spermatogenesis of the first reproductive cycle (RC) proceeded in control fish. However, only protease and antiprotease activities showed different level at different stages of the second RC in control fish, but showed scarce disruption in fish treated with EE₂ or Tmx. Peroxidase and bactericide activities are more sensitive to EE₂, than to Tmx. The effects induced by EE₂ varied depending on the activity analyzed, the dose and the time of exposure and the reproductive stage and the age of the specimens.