Abstract: This study evaluated the effects of replacing soybean meal (SBM) with cowpea meal (CM) on growth performance, intestinal morphology, liver health, and amino acid metabolism in channel catfish (Ictalurus punctatus). Four isonitrogenous (37% crude protein) and isolipidic (8% crude lipid) diets were formulated, in which CM replaced 0, 10%, 20%, and 30% of SBM, designated as CON, R10, R20, and R30, respectively. A total of 240 juvenile channel catfish initial body weight: (22.44±0.28) g were randomly distributed into 4 groups with 3 replicates each and fed with the experimental diets for 8 weeks. The results showed that the weight gain rate of the R10 and R20 groups was significantly higher than that of the CON group. The specific growth rate of each substitution group was significantly higher than that of the CON group. However, Feed intake in the R10 group was significantly higher than that in the other groups (P<0.05), and a dose-dependent decrease in feed intake was observed with the increasing CM substitution levels. Histopathological examination of intestinal sections stained with hematoxylin and eosin (H&E) showed that dietary CM supplementation significantly increased the goblet cells to villus height ratio, villus height, and muscle layer thickness in the R20 group was significantly higher than that in the CON group (P<0.05). In contrast, H&E and TUNEL staining of liver tissues revealed no noticeable signs of inflammation or apoptosis. Moreover, the transcriptional expressions of protein synthesis-related genes (mtor, p70s6k, eif2b) exhibited an upregulation trend. In summary, replacing up to 30% of dietary SBM with red cowpea meal did not impair growth performance or liver protein metabolism in channel catfish, while it improved intestinal morphological structure.