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In order to study the effects of dietary β-glucan (BG), vitamin C (VC) and their combination (BG/VC) on growth, humoral and mucosal immune responses of red sea bream ( Pagrus major ) and its resistance to low water salinity stress, 240 healthy fish with initial body weight of 1.98 ± 0.01 g were randomly divided into four groups: a control group fed with basal diet and three treated groups fed with basal diets supplemented with 1000 mg kg − 1 BG, 800 mg kg − 1 VC, and the combination of 500 mg kg − 1 BG + 400 mg kg − 1 VC, respectively. The obtained results showed that, compared with the control, the final body weight, weight gain and specific growth rate, feed and protein efficiency ratio, body protein content, nitro blue tetrazolium (NBT), total serum protein and tolerance against low salinity stress increased in fish fed BG or/and VC supplementations with the highest being in fish fed both BG and VC supplements while body moisture content, plasma glucose, triglyceride and malondialdehyde (MDA) contents decreased ( P < 0.05); body lipid content, hematocrit, serum and mucus lysozyme activities, superoxide dismutase (SOD), alternative complement pathway and mucus secretion also significantly increased in fish fed BG and VC supplements ( P < 0.05). Moreover, the fish fed BG diet had better improvement ( P < 0.05) in mucus bactericidal activity than the VC group. Furthermore, fish fed BG diet exhibited higher serum peroxidase activity (PA), however, fish fed VC diet showed higher mucus PA than the control group ( P < 0.05). Thus, the basal diet supplemented with BG or/and VC could promote the growth, antioxidant capacity, humoral and mucosal immune responses of red sea bream, and enhance the resistance to low salinity stress. Statement of relevance A combination of β-glucan and vitamin C presented an additive effect on inducing the growth, immune responses and oxidative status of red sea bream. We recommend that treatment of 500 mg of β-glucan and 400 mg of vitamin C per kg diet is the appropriate concentration of inducing the red sea bream immune response. [ABSTRACT FROM AUTHOR]