Abstract:A 2×3 two-factorial experiment was designed to investigate the effects of dietary administration of Bacillus subtilis and yeast culture on growth, serum biochemical indices, antioxidant capacity, and disease resistance of juvenile hybrid grouper (Epinephelus fuscoguttatus♀×E. lanceolatus♂) [initial weight: (23.41±0.47) g]. Nine isonitrogenous and isoenergetic diets were formulated with three levels of B. subtilis [0 (control), 0.5%, and 1.0%], and each B. subtilis level was formulated with three yeast culture levels [0 (control), 0.5%, and 1.0%]. Juvenile hybrid groupers were fed for 8 weeks. The results showed that the interaction between B. subtilis and yeast culture had no significant effects on the survival (SR) and weight gain rate (WGR) of grouper (P>0.05). The WGR of Y1B1 and Y1B2 groups was significantly higher than that of the control and Y2B2 groups (P<0.05).The interaction between B. subtilis and yeast culture had a significant effect on the aspartate aminotransferase (AST) and alkaline phosphatase (AKP) in the serum of grouper (P<0.05); the AST and AKP activities in the serum of Y1B1 and Y1B2 groups were significantly lower than those in the control and Y2B2 groups (P<0.05). The interaction between B. subtilis and yeast culture had a significant effect on the superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the intestinal tract of grouper (P<0.05), but no significant interaction with catalase (CAT) or total antioxidant capacity (T-AOC) in the intestinal tract (P>0.05). The activities of SOD, CAT, and T-AOC in the intestinal tract of the Y1B1 and Y1B2 groups were significantly higher than those in the control and Y2B2 groups (P<0.05), but the MDA content in the intestinal tract showed an opposite trend to SOD (P<0.05). There was no interaction between the effects of dietary B. subtilis and yeast culture on the cumulative survival rate of juveniles challenged with Vibrio anguillarum (P>0.05). The highest value of cumulative survival rate of juveniles was found in the Y1B1 group, which was significantly higher than that in the control group (P<0.05). In conclusion, supplementation of 0.5% or 1.0% B. subtilis and 0.5% yeast culture in diets could promote WGR, antioxidant capacity, and disease resistance in juvenile hybrid grouper.