We evaluated the acute toxicity of copper on the survival rate of Coilia nasus fingerlings and on antioxidant enzyme (Superoxide dismutase, SOD; Catalase, CAT) activity changes in fish liver. The histology of experimental fish gills and liver were also analyzed. Fish were exposed to copper sulfate (CuSO₄) solution with Cu²⁺concentrations of 0(control), 0.3, 0.54, 0.96, 1.68 and 3 mg/L. The 50% lethal concentration (LC₅₀) values of copper on C. nasus were 1.087, 1.062, 1.042 and 0.9 67 mg/L at 24, 48, 72 and 96 h, respectively. The safe concentration of copper for this species at the fingerling stage was calculated as 0.009 67mg/L. The activities of CAT and SOD were significantly enhanced in liver cells after the fish were exposed in CuSO₄ for 12 and 24 h compared with those in the control group (P<0.05). Forty-eight hours later, the activities of CAT started to decline, while the activities of SOD did not decrease until 72 h. Overall, the CAT (after 48 h) and SOD (after 72 h) in the liver cells of fish exposed to copper sulfate exhibited lower activities than those in the control group. The changes of CAT activities after 48 h positively correlated with Cu²⁺concentration. Our results indicated that 1.68 mg/L Cu²⁺was toxic to Coilia nasus fingerlings, resulting in swollen and denatured epithelium and deformed lamellae of the gills. The hepatic ultrastructural observation sampled from the fish exposed to 3 mg/L Cu²⁺showed significant hypertrophy of liver cells; the mitochondria exhibited vacuolization; vacuoles and lipid droplets occurred in cytoplasm. Copper appeared to induce fatty liver syndrome. We concluded that determining antioxidant enzyme (SOD and CAT) activities and histopathological analysis are important approaches to evaluate the safe concentration of copper for C. nasus fingerlings.