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Many diets employed in aquaculture are enriched with selenium to improve the diet quality and its conservation. The aim of the study was to investigate the effects of a diet enriched in selenium (1.21mgkg−1) on the antioxidant response of Procambarus clarkii (Girard, 1852). Crayfish fed a diet with lower selenium content (0.30mgkg−1) were the control. Selenium accumulation, enzymatic activities, and total glutathione were evaluated in hepatopancreas of adults of both sexes fed with both diets for 50 days at two experimental times (T 30, T 50 days). Treated females exhibited the highest selenium bioaccumulation during both experimental times, while treated males displayed the highest selenium concentration after 30 days, compared to control crayfish. A sex-related difference was found for the response of the analyzed enzymes in the selenium diet-treated specimens. In fact, superoxide dismutase, glutathione peroxidase and glyoxalase I activities in males were more sensitive compared with females, showing depleted activities in both experimental times. Catalase activity was induced in females (T 50), while glutathione S-transferase activity was the highest in treated females and the lowest in treated males, compared with own controls. Only glutathione reductase activity and glutathione content showed the same trend in both sexes, which were both lowered in treated specimens, when compared with control crayfish. This result might be due to the effect of selenium toxicity on this freshwater species. Males and females of P. clarkii showed a different susceptibility to the prooxidant effects in a Se-enriched diet. [Copyright &y& Elsevier]