Red sea bream (Pagrus major) were fed β-glucan (BG) or vitamin C (VC) alone or in combination. The mixture supplementation significantly improved growth performance and feed utilization of fish. Fish fed BG or/and VC supplementations showed enhanced oxidative status and tolerance against stress. Fish fed BG or/and VC supplementations showed enhanced humoral and mucosal immune responses. BG and VC synergistically enhance the performances of red sea bream.