Alterations in the biochemical composition, growth and histological structure of the gills of  fish Oreochromis niloticusfollowing prolonged exposure (112 days) to a sub lethal concentration of copper (0.043 ppm), were investigated. The tissue levels of total proteins, total lipids and total carbohydrates were decreased while muscle glycogen level was increased after was decreased significantly during copper exposure indicating that the organic matter (biochemical content) might be involved in the energy expenditure. The exposed to copper. Muscle glycogen change may give a good tissue total values of proteins, lipids and carbohydrates seem to be of limited value as potential stress in indicators in fish estimate of a stress condition. Copper had resulted in an extracted appearance in gill lamellae; adjacent lamellae fused together and the epithelial lining of lamellae became disintegrated. Growth, behavioral and histological responses were integrative to the biochemical changes. To sum up, the consistent changes in the biochemical composition, growth rate, behavior and histological structure noted in O. niloticus after 112 days exposure to the sublethal concentration of copper indicate that these fish have not acclimated to copper.