The study was conducted to determine the effects of waterborne Cu exposure on physiological, biochemical, and gene expression related to lipid metabolism in via a 96 h acute toxicity experiment. In the present study, were respectively exposed to 0 (control), 0.1 mg Cu/L, and 0.2 mg Cu/L (96-h LC₅₀). The results showed that Cu accumulation in liver, muscle, and whole fish increased with increasing Cu concentration. The order of Cu accumulation was liver>whole body>muscle at the same Cu dose. With the increase in Cu concentration, malondialdehyde (MDA) content and activities of antioxidant enzymes[glutathione peroxidase (GSH-PX), total superoxide dismutase (SOD), and catalase (CAT)] increased in the liver. Acute Cu exposure induced blood cells deposition in veins and dilatation of sinusoids in the liver, and also induced epithelial hyperplasia, clubbed tips, and aneurysms in gills. In the gut, amylase activity increased significantly, yet the lipase activity decreased after acute Cu stress in . In the liver, activities of amylase, protease, and lipase decreased significantly with the increase in Cu concentration. The expression of genes involved in lipogenesis () under 0.1 mg Cu/L exposure was the highest. However, the expression of genes involved in lipolysis () was the highest in the 0.2 mg Cu/L treatment group. Acute Cu stress had no significant influence on transfer factor was significantly up-regulated relative to that of the control. This study revealed the significant effects of Cu exposure on physiological, biochemical, and gene expression related to lipid metabolism in , which provides beneficial guidance for the rational use of Cu in the production process of , and also provides beneficial references to technical indicators for better monitoring of heavy metal pollution in fish production.