Copper-oxide and dibutyltin are used as antifouling underwater hall paints. Copper-oxide nanoparticles (CuO-NPs) are serious water pollutants but their impact in fish?s performance remains poorly understood. In the present study we have investigated the effects of different concentration of copper oxide nanoparticles (CuO-NPs) and Dibutyltin on Tilapia fish and their bioaccumulation in the gills, liver and brain and also to check minimum lethal dose. We have exposed Mozambique Tilapia (Tilapia mossambica), a freshwater edible fish to different doses of copper nanoparticles (15mg/L, 10mg/L, 5mg/L, 2mg/L) and Dibutyltin (0.08mg/L, 0.04mg/L, 0.12mg/L) for 96 hours. The results indicated that the activity of oxidative stress enzymes GSH, AChE and glutathione -S-transferase were significantly decreased. The results showed more serious deleterious impart in the tissues in case of CuO-NPs than dibutyltin which may affect fish growth and development, protein content and causes death. The GST level in liver was maximum affected, when fish treated with CuO-NPs at 10mg/L and dibutyltin at 0.04mg/L. In case of gills GST, CuO-NPs at a concentration of 15mg/L was more deleterious. The level of AChE was more affected in gills and brain when treated with CuO-NPs at 15mg/L. In CuO treated with 10mg/L, the GSH level was maximum affected in liver and gills. In CuO treated with 10mg/L, the protein content was maximum reduced in liver and brain but in gills at 15mg/L. In case of dibutyltin treated with 0.12mg/L, liver, gills, brain most affected. The present study investigated that CuO NPs are more toxic than dibutyltin.