Abstract: Excessive environmental heavy metals can induce lipid accumulation and cause hepatopancreas and spleen damage of fish. In order to explore the effects of different concentrations of Copper (Cu) on growth performance, hepatopancreas lipid metabolism and spleen immunity, tilapia initial weight of (0.45±0.02) g were randomly assigned to 0 (control), 0.2, 0.4 and 0.8 mg/L Cu concentration, respectively. After four-week cultivation, hepatopancreas, serum, and spleen were sampled. The results showed that: 1. Under waterborne Cu exposure, the survival, weight gain, and specific growth rate of the tilapia showed a significant decline. The hepatosomatic index of tilapia in the 0.4 and 0.8 mg/L Cu concentration groups were significantly higher than those in control and 0.2 mg/L group (P<0.05). 2. Compared to control, triglycerides contents in hepatopancreas of tilapia under 0.4 and 0.8 mg/L groups increased significantly (P<0.05), and no significant difference was found in 0.2 mg/L group. There was no significant difference of total cholesterol content (T-CHO) and 3-hydroxy-3-methylglutaryl-Coenzyme A reductase activity in hepatopancreas among all groups (P>0.05). 3. Under Cu exposure, serum low-density lipoprotein cholesterol, T-CHO content and aspartate aminotransferase activity (P<0.05) were significantly higher than that of control group. Serum triglyceride content decreased significantly thereafter increased with the highest value in 0.8 mg/L group (P<0.05). The alanine aminotransferase activity of tilapia under 0.8 mg/L group was significantly higher than 0.2 and 0.4 mg/L groups (P<0.05), but had no significant difference of control. 4. The histological analyses indicated that the hepatopancreases tissue of tilapia showed vacuolization seriously, and the lipid droplets content was significantly higher than that in control. Environmental copper also caused more and larger melano-macrophage centers (MMCs) in spleen, and lipofuscin increased remarkably within MMCs. The results suggested that waterborne Cu exposure significantly reduced the growth performance of tilapia, and caused lipid deposition in hepatopancreas and serum, further induced hepatopancreas and spleen damage. This study provided basic date for clarifying abdominal lipid accumulation and spleen histological injury in aquaculture species under heavy metal environment.