The effects of dietary supplementation with Bacillus licheniformis FRI MY-55 and its fermented products, lactosucrose and levan, on short-chain fatty acid and lactic acid in feces, immune status, and pathogen resistance of the spotted grouper Epinephelus coioides were investigated. Spotted grouper were fed diets supplemented with B. licheniformis FRI MY-55 + lactosucrose and B. licheniformis FRI MY-55 + levan for up to 10 weeks. The total short-chain fatty acid and lactic acid levels in feces of the fish fed experimental diets for 5 and 10 weeks were significantly higher compared to those of the control group. Before and after Vibrio harveyi challenge, lysozyme activity of the experimental groups was significantly higher than that of the control group (p < 0.05). After V. harveyi challenge, the respiratory burst and survival rates of the fish fed experimental diets were significantly higher than those of the control group (p < 0.05). Overall, the results of this study indicate that dietary administration of B. licheniformis FRI MY-55 and its products, lactosucrose and levan, enhances the pathogen resistance of orange-spotted grouper.