Today, human effects due to industrial development and population increase caused water ecosystems to be polluted by various pollutant such as heavy metals. Serum biochemical parameters are widely used in blood analysis and these parameters are suitable indicators for monitoring physiological changes in fish. Hence, the aim of present study to the effects of waterborne copper on serum glucose, total protein, albumin and triglyceride levels and serum cholinesterase (ChE), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkalane phosphatase (ALP) and lactate dehydrogenase (LDH) activities of O. niloticus were determined after exposing the fish to 10, 50 and 100 µg/L copper applied as CuO nanoparticles (CuO NPs) and CuSO4 over 1, 7 and 15 days.No mortality was observed during the experiments. Serum glucose and albumin levels increased while serum total protein, cholesterol and triglyceride levels decreased compared to control at the end of the 15th day. There was also a decrease in serum ChE activity whereas serum AST, ALT, ALP and LDH activities increased. Overall, CuSO4 and CuO NPs had similar effects in serum parameters of O. niloticus.