Copper accumulation in the gill, liver, kidney, spleen, and muscle tissues of Oreochromis niloticus was determined after exposing the fish to 10, 50, and 100 mu g Cu/L applied as copper sulphate (CuSO4) and copper oxide nanoparticles (CuO NPs) after 1, 7, and 15 days. Changes in the liver SOD, CAT, and GPx activities influenced by this accumulation were also studied. No mortality was observed during the experiments. Copper levels increased in the gill, liver, kidney, and spleen tissues of O. niloticus compared to control when exposed to both CuSO4 and CuO NPs, whereas no accumulation was detected in muscle tissue at the end of the exposure period. Highest accumulation of copper was observed in the order of the liver, kidney, spleen, and gill tissues, respectively. SOD, CAT, and GPx activities increased in the liver tissue at the end of the exposure period. Overall, CuO NPs are more effective than CuSO4 in terms of tissue accumulation and liver enzyme activities.