The aim of this experiment was to investigate the effects of high-fat diets on the short-term growth performance and antioxidant capacity of pearl grouper to help formulators and farmers anticipate the possible negative effects of high-fat diets on grouper growth and take effective measures in the formulation and feeding schedule of high-fat diets. Seven groups of isonitrogenous diets with fat levels of 8% (EE8), 10% (EE10), 12% (EE12), 14% (EE14), 16% (EE16), 18% (EE18), and 20% (EE20) were fed to pearl grouper (initial mean weight: 13.70±0.01g) for 4 weeks with a crude protein level of 48%. The experimental results showed no significant change in weight gain rate (WGR) and survival rate (SR) as the level of dietary ether extract increased (P＞0.05), while the feed intake was significantly lower in the EE14-EE20 group (P＜0.05); further, the viscerosomatic index (VSI) and protein efficiency ratio (PER) increased significantly (P＜0.05) after the dietary ether extract exceeded 16%. The EE14-EE20 group had a significantly higher abdominal muscle ether extract (AMEEC) (P＜0.05), and the EE16-EE20 group had a significantly greater hepatosomatic index (HSI) (P＜0.05). Compared to the EE12 group, total cholesterol (T-CHO) was significantly higher in the EE8, EE10, EE18, and EE20 groups (P＜0.05); glutathione peroxidase (GSH-PX) activity was significantly lower in the EE16-EE20 group (P＜0.05); malondialdehyde (MDA) content was significantly higher in the EE20 group (P＜0.05); and vacuolated area and hepatocytes in the EE8 and EE16-EE20 groups’ lipid droplet amount were significantly increased (P＜0.05). The relative expression of the lipid synthesis genes g6pd, 6gpd, and me was significantly increased in the EE20 group (P＜0.05), and the lipolytic genes cpt-1 and pparα were significantly increased in the EE16-EE20 group (P＜0.05). The results have shown that dietary ether extract above 16.77% causes fatty deposits in the liver of pearl amberjack, reducing the liver’s antioxidant capacity and impairing liver health.