Long-term feeding of fish with a high-fat diet (HFD) causes excess fat deposition and an impairment of immune function. In the present study, we aimed to determine whether dietary tea polyphenols (TPs) would ameliorate the adverse effects of HFD-feeding in GIFT tilapia. Juvenile GIFT tilapias (5.4 ± 0.9 g) were raised in twelve 200-L tanks (three tanks per diet, 20 fish per tank) and fed a control diet (6% fat, 36% protein), an HFD (12% fat, 36% protein), or an HFD supplemented with 50 mg/kg or 200 mg/kg TP for 8 weeks. The fish were hand-fed 5% of their body weight per day in three feeds, and maintained at 28 ± 1 °C under a 14-h light/10-h dark cycle. The fish in each tank were bulk weighed and counted fortnightly, and the daily feed amount was adjusted accordingly. At the end of the trial, the cumulative survival rate was calculated, and the weight gain and feed conversion ratio were calculated according to the bulk weight of fish in each tank. Tissues were collected from nine fish per diet, their organs were weighed, and biochemical and molecular indices were subsequently measured. HFD-feeding significantly increased lipid deposition, reduced cumulative survival from 96% to 75%, reduced hepatic alkaline phosphate activity (AKP) and serum total antioxidant capacity (T-AOC); and reduced the hepatic expression of immunoglobulin M (IgM), transforming growth factor-beta (TGF-β) and glutathione-S-transferase (GST) genes versus the control diet. The addition of TPs at 50 or 200 mg/kg both ameliorated the HFD-induced increase in lipid droplets in the liver (50 mg/kg TP from 40.83% to 17.27%; 200 mg/kg TP to 25.33%), and increased the cumulative survival rate of the tilapia. The addition of 50 mg/kg TP had a marked effect increasing cumulative survival to 90%, and increasing the activities of serum acid phosphatase (ACP), T-AOC; and IgM, TGF-β, nuclear factor-κB (NF-κB), superoxide dismutase (SOD), and GST gene expression to the highest level of the HFD-fed groups. The 50 mg/kg TP-containing diet also significantly increased the hepatic expression of carnitine palmitoyltransferase 1 alpha (CPT1α) versus the control diet. In contrast, the tilapia fed an HFD supplemented with 200 mg/kg TPs had the lowest expression of adipose triglyceride lipase, hormone-sensitive lipase, CPT1α, fatty acid synthase and acetyl-CoA carboxylase alpha genes of any of the groups, which implies that the lower and higher levels of TP supplementation have differing effects on lipid metabolism. The 200 mg/kg supplement had lower cumulative survival rate (82%), and smaller effects on serum ACP and hepatic AKP activities than the 50 mg/kg dose, and had no significant effect on serum T-AOC or the expression of IgM, TGF-β, GST, or NF-κB genes in the tilapia. These results indicate that the beneficial effects of TPs on the lipid metabolism and health of fish fed an HFD are dose-related. Moreover, they are likely to be largely mediated through lipid catabolism.