In this study, nine experimental diets were formulated to contain three graded levels of protein (40, 45 and 50% of dry diet) and three graded levels of cellulose (0, 5 and 10% of dry diet). These diets were then fed in triplicate to yellow catfish for 90 days. We found that fish fed diets containing 45% and 50% protein had more weight gain than did fish fed a 40% protein diet, while fish fed diets supplemented with 5% cellulose achieved the greatest weight gain and the lower feed conversion ratio. We found that as dietary cellulose and protein levels were increased, the activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), immune response parameters (alkaline phosphatase, acid phosphatase, phagocytic index, respiratory burst, complement 3 and 4) and the mRNA level expression ofcopper/zinc superoxide dismutase,catalase,glutathione peroxidaseandglutathione reductaseall rose. In contrast, rising cellulose levels were associated with decreased malondialdehyde contents and increasingtumour necrosis factor,interleukin 1andinterleukin 8mRNA expression. Overall, our results indicate that dietary protein supplementation can enhance yellow catfish immune functionality and that while dietary protein impacts on the immune response are influenced by dietary cellulose levels, increased dietary cellulose was associated with inflammatory gene upregulation.