Abstract The main objectives of this study were to evaluate the effect of partial and total replacement of fish meal (FM) protein by cow pea seed meal (CPSM) protein in practical diets on growth performance, feed utilization, and body composition of Nile tilapia, Oreochromis niloticus (L.). Fish of an average initial weight of 4.6 ± 0.2 g were stocked in 15 glass aquariums (80 L each) at a rate of 15 fish per aquarium. FM protein (30% of the diet) was used as the sole source of animal protein in the control diet. Percent replacement of FM by CPSM on the basis of crude protein were as follows: 0% (control diet A), 25% (diet B), 50% (diet C), 75% (diet D), and 100% (diet E). Diets were fed to fish at a rate of 4% of the total fish biomass daily, for a period of 16 wk. The results of this study revealed that the fish fed control diet A (100% FM) had the best average final body weight, specific growth rate (SGR %/d), weight gain (g/fish), weight gain %, while the poorest results for all parameters were obtained with fish fed diet E (100% CPSM). The same parameters of fish fed diets B (25% CPSM) and C (50% CPSM) were not significantly different (P > 0.05) from those of fish fed the control diet A. Feed utilization parameters of fish fed diets A, B, C, and D were better than for diet E. Proximate composition of whole‐body moisture and ash contents were not significantly different (P > 0.05) among all experimental diets and control diet. Whole‐body protein contents for fish fed diets B and C were superior to the control diet A. Incorporation of CPSM in the diets significantly increased whole‐body fat content. Incorporation of CPSM in the diets significantly decreased apparent digestibility coefficient of crude protein crude fat and energy. Diets B and C were not significantly different from control diet A. Therefore, these findings suggest that up to 50% of FM protein can be replaced by CPSM protein in Nile tilapia diets without any adverse effects on growth performance, feed utilization, body composition, and digestibility.