The current study has determined the toxicity effects of copper nanoparticles (CuNPs) on the some vital organs such as gill, liver and kidney of Caspian Roach; Rutillus rutillus caspicus. For this purpose, 120 fishes were used as experimental fishes and exposed to 0.1, 0.2 and 0.5 mg/L of Cu nanoparticles for 21 days, and 30 fishes as control. The mean water temperature of the aquaria was 22±2 ºC, dissolved oxygen 5.2 mg/L, pH at 7±0.004 and the concentration of Calcium Carbonate was 270 ppm. On the 7, 14 and 21 days after exposing the fishes to CuNPs, three fish were randomly selected from each aquaria, sacrificed and samples from their liver and blood were taken. Changing in antioxidant enzymes level were determined by evaluation of superoxide dismutase (SOD) and catalase (CAT) activities in the blood of fish. In first week, the samples that exposed to 0/1 mg/L of CuNPs concentration had more activities in SOD and CAT levels (p<0.01) but other treatments (0.2 & 0.5 mg/L) didn’t have any increase in enzyme activities. The liver microscopic sections were prepared and stained by H&E method and examined by light microscope which showed histological alternations in the liver tissues. Histological changes in liver included blood congestion in the central veins, cytoplasmic vacuolation of the hepatocytes, cellular hypertrophy, congestion in the blood sinusoids and necrosis of the hepatocytes and nuclear pyknosis. The degree of damages was more intensive at higher CuNPs concentrations. Evaluation of these changes could be useful in estimating the harmful effects of CuNPs. The result of the study showed that CuNPs could cause decrease in antioxidant enzyme activities and severe damages in the liver tissues of Caspian roach; Rutillus rutillus caspicus and have lethal effects for fish.