Female catfish, Clarias gariepinus, which were collected from the Nile River at Assiut region, were divided into 7 groups The first group was left as control, the second was treated with mercuric chloride (MC) for three weeks following by normal water for one week. The third , fourth and fifth groups were provided by MC (150 µg/ L of water). This treatment was continued for three weeks. Then these fish were received CN instead of MC, for one week, with 15 and 25 mg CN respectively / 100 g wet food. The fifth fish group received diet supplemented with vit E (α-tocopherol) (100 mg/kg wet diet), for one week, instead of MC treatment. Vitamin E was used as standard antioxidant drug. Following three weeks of normal ambient water, the sixth and seventh aquaria received only CN for one week, with 15 and 25 mg CN respectively / 100 g wet food, respectively. At the end of the experiment, Samples of liver, kidneys (posterior part), gills (right gills) and ovary were excised. The measurement included the oxidative stress parameters: carbonyl protein and total peroxide and the antioxidant enzyme activities superoxide dismutase (SOD), catalase (CAT) and glutathione-s-transferase (GST) in all selected organs. MC treatment induced harmful effect in fish, probably due to its enhancing effect on reactive oxygen species (ROS) production in fish organs especially the respiratory and osmoregulatory organs namely gills. The result suggests that this gill damage may exert hypoxic case, anoxia for different organs and some Cu excretion resulting in a magnification of ROS overproduction. Also, the observed oxidative stress in ovary tissue of MC-treated fish may affect fish fertility. The addition of CN in fish diets could protect the fish C. gariepinus against MC-induced oxidative damage showing recovery of fish organs. It could suggest that the detoxifying mechanism of action of CN is mainly due to its scavenging activity of free radicals rather than tissue healing.