This study aimed to investigate the effects of fishmeal (FM) replacement by rice protein concentrate (RPC) with a xylooligosaccharides supplement on the growth performance, antioxidant capability and immune response against Aeromonas hydrophila in blunt snout bream (Megalobrama amblycephala). Fish (46.85 ± 0.34 g) were randomly assigned to one of 6 diets, namely the control diet (containing FM), the RPC diet (FM replaced by RPC) and RPC diet supplemented with 0.5, 1.5, 2.3 and 3% XOS respectively, for 8 weeks. After the feeding trial, fish were challenged by Aeromonas hydrophila for 96 h with the blood and liver sample obtained at 48 and 96 h respectively. The results showed that the final weight, weight gain and protein efficiency ratio of fish fed RPC diet were significantly (P < 0.05) lower than that of the control group, whereas the opposite was true for FCR. However, the supplement of 1.5% XOS remarkably (P < 0.05) improved these parameters compared to the control diet. Plasma total iron binding capacity of fish fed the RPC diet showed little difference (P > 0.05) with that of the control group, but it enhanced significantly (P < 0.05) with the supplement of 1.5% XOS compared to the control group. After bacterial infection, plasma lysozyme (LYM), complement 3, complement 4, myeloperoxidase (MPO), acid phosphatase (ACP) and alkaline phosphatase activities, as well as immunoglobulin M, levels all increased significantly (P < 0.05) with the maximum value is attained at 48 h, then they decreased significantly (P < 0.05) with further increasing time at 96 h. Similar results were also observed in liver superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities as well as malondialdehyde (MDA) content. Regarding dietary treatment, these parameters of fish fed RPC diet showed little difference (P > 0.05) with those fed the control diet but were significantly enhanced (P < 0.05) when RPC diet was supplemented with 1.5–2.3% XOS, except for hepatic (MDA) content which showed an opposite trend compared to the control group. After 96 h of challenge, the relative percentage survival (RPS) of fish fed XOS was significantly higher (P < 0.05) than that of fish offered the control and RPC diet. In addition, significant (P < 0.05) interactions between dietary XOS and sampling time were also observed in plasma LYM, MPO, ACP, and hepatic SOD, CAT, GPX, MDA, as well as RPS. In conclusion, this study indicated that dietary supplementation of 1.5%XOS could significantly improve the growth performance, antioxidant capability, innate immunity and A. hydrophila resistance of blunt snout bream fed diets with FM replaced by RPC.