Copper is one of the most toxic metals to fish and causes cytotoxic, mutagenic and carcinogenic effects. The accumulation of copper in an aquatic environment directly impacts man and the aquatic ecosystem. The present study aimed to determine the effect of copper sulphate (CuSO4) accumulation on the induction of micronuclei in blood and histological changes in kidney and liver of the fish Channa punctatus. The test chemical LC50 was determined after 96 hours during the first experiment. Later in the second experiment, the test animal was exposed to three sub-lethal concentrations of CuSO4 [0.1 mg/l (96 h-LC50/40), 0.2 mg/l (96 h-LC50/20) and 0.4 mg/l (96 h-LC50/10)]. Physico chemical parameters of the test medium, such as pH, temperature, hardness, alkalinity, and dissolved oxygen, were observed throughout the experiment, and all values were within the ranges necessary for the fish's survival. At intervals of 7, 14, 21, and 28 days, the control (without any test chemical) and copper sulphate exposed Groups' blood, liver, kidney, and gill tissues were taken to evaluate changes in genotoxic and histological parameters. Micronuclei (MN) induction and nuclear abnormalities (NAs) were observed at regular intervals. After 28 days, the MN frequency in Groups 1, 2, 3, and 4 was 0.78±0.006, 8.40±0.052, 10.37±0.098 and 10.90±0.024 respectively. A significant (P< 0.05) rise in MN frequencies and NAs indicated fish erythrocytes' DNA damage. Histological analysis of the liver, kidney, and gills revealed serious tissue injury such as necrosis, vacuolization, and degeneration after 28 days in the exposed Groups. The present study observed changes due to genotoxicity and histology, giving the most comprehensive understanding of CuSO4 stress on the fish C. punctatus and its risks to human health.