Two pond experiments were conducted to evaluate cottonseed meal (CSM), distiller’s dried grains with solubles (DDGS), and supplemental lysine as replacements for soybean meal (SBM) in channel catfish diets. In Experiment 1, fish fed diets in which SBM was totally replaced with CSM gained similar weight as fish fed control diet, but fish fed CSM diet in Experiment 2 had 9.5% lower weight gain than fish fed control diet. In both experiments, feed conversion increased significantly for fish fed CSM diet. There were no consistent trends in body composition of fish fed CSM diet versus control diet. Fish fed the DDGS + SMB diet had higher (Experiment 1) or similar (Experiment 2) weight gain than fish fed control diet. Feed conversion ratio was significantly lower in both experiments for fish fed SBM + DDGS diet than that of fish fed control diet. Body fat tended to be higher in fish fed SBM + DDGS diet compared to fish fed control diet. It appears that about 50% of SBM can be replaced with CSM + lysine in catfish diets without negatively affecting fish performance. Further, DDGS can be used up to at least 30% when the diet is supplemented with lysine.