The current study investigated the bioaccumulation of heavy metals, as well as, physiological and histological alterations, in gonads of Catfish (Clarias gariepinus) inhabiting the polluted location (main basin) and a relatively clean area (southwest basin) at Lake Maryout. A significant (P<0.05) decrease was recorded in muscle total protein and lipid in fish collected from the main basin in comparison to the southwest basin. In contrast, a significant (P<0.05) increase in muscle water content was detected in fish collected from the main basin. A significant (P<0.05) decrease in LH, FSH, estrogen, and progesterone hormones, as well as the activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), were detected in fish collected from the main basin in comparison to the southwest basin. Histological observation of ovary showed lytic ovary with some stages of oocytes include early pre-vitologenic, atretic late pre-vitologenic, wide inter-follicular space and loose tunica albugenia. On the other side, testes pathologies showed completely disorganized lobule structure, accompanied by a reduced number or disappeared of germinal cells, increased interstitial space with reduced interstitial cells.  In conclusion, this study confirmed that the main basin of Lake Maryout suffered from great pollution that affected completely on the fish population and the situation needs the rapid intervention of the Egyptian government to stop agricultural, industrial and health drainage in Lake Maryout by establishing treatment units before direct drainage in the Lake