An eight-week feeding trial was carried out to evaluate the influence of vitamin E (V_E) on the growth performance, antioxidation and immunity of hybrid grouper juveniles (Epinephelus fuscoguttatus ♀×E. lanceolatus ♂). Six isoenergetic (340 kcal/100 g dry matter), isoproteinic (51.5% of dry matter) and isolipidic (9% of the dry matter) diets were formulated to contain graded levels of V_E (4.1, 26.3, 40.7, 57.1, 116.8, 209.6 mg/kg, dry matter basis). Triplicate groups of twelve fish [initial average weight of (14.22±0.01)g] were stocked into floating cages and offered their prescribed diet twice daily (8:00 and 16:30) to apparent satiation. After the growth experiment, the remained experimental fish from each group were used for a 72 h copper challenge. Results showed that fish fed 57.1 mg/kg V_E exhibited higher weight gain percentage (WG) than fish fed 4.1 mg/kg V_E. Whereas, condition factor (CF), hepatosomatic index (HSI) intraperitoneal fat (IPF) values remained non-significant among all dietary groups. Whole-body and muscular compositions (moisture, protein and lipid) did not show significant differences among all dietary groups. Fish fed 209.6 mg/kg V_E had higher hepatic V_E concentration than fish fed 4.1 mg/kg V_E. The total-antioxidant capacity (T-AOC) of liver, serum lysozyme (LZM) and immunoglobulin (IgM) concentrations were increased with the increasing V_E levels, reaching a peak value at the 57.1 mg/kg level, and thereafter, it started to decrease as dietary V_E level further increased. After the challenge, the survival rate of the experimental fish fed with 40.7, 57.1 or 116.8 mg/kg V_E diet was higher than that of the experimental fish fed with 4.1 mg/kg V_E. The relative expression of nuclear factor E2-related factor 2 (Nrf2) in head kidney of fish fed 4.1 mg/kg V_E was lower than that of fish fed 40.7, 57.1 or 116.8 mg/kg V_E. Generally, the analysis of a quadratic broken line model based on WG and T-AOC indicated that the optimal dietary V_E requirement of hybrid grouper juvenile was found to be 62.92 mg/kg and 86.25 mg/kg dry matter, respectively.