Copper and zinc are needed as essential nutrients for plants, animals, and human’s daily basic activity, however, at high concentrations and prolonged exposure they bring harmful effect to life creature and the environment. Thus, this study aimed at finding out the toxicological impact of copper and zinc on liver and gill tissues of Oreochromis mossambicus. This study used 21 male tilapia (60-100 grams), which grouped into 7 treatment groups, K1 was negative control; K2, K3, and K4 were exposed to 1, 2.5, and 5 mg/L CuSO₄; K5, K6, and K7 were exposed to 2.5, 5, and 7.5 mg/L ZnCl₂, respectively, for 15 days. Fish liver and gill were collected for histopathological procedure using hematoxylin-eosin. The results showed similar figure of tissues damages between treatment groups, including melanomacrophage center, vacuolar degeneration, cell necrosis, and hemorrhage. The spreading of MMCs in the liver tissue of tilapia fish exposed to copper was higher than in zinc exposure. In gills tissue, several minor, moderate, and severe changes were observed, revealed that the higher the concentration of CuSO₄ and ZnCl₂ exposure the more severe the tissue damage observed. In conclusion, both CuSO₄ and ZnCl₂ exposure changes the histopathology of liver and gill of tilapia fish.