The present study was designed to investigate the effect of incorporation of cotton seed meal CSM in the diets of Nile tilapia Oreochromis niloticus. A set of 108 fish of O. niloticus L. mono-sex male fingerlings with average initial weight of 11.60 ±0.72 g was used in this trail. Twelve fish were randomly stocked into each aquarium with three replications for each treatment and fed the experimental diet (295 g kg^-1 crude protein) and isocaloric (18.76 MJ kg^-1 gross energy). The first diet CSM1 which contained (fish meal : cotton seed meal 2:1), the second CSM2  which contained (fish meal : cotton seed meal 2:2) and the third CSM3 which contained (fish meal : cotton seed meal 1:2). Results of the present experiment indicated that, inclusion of cotton seed meal CSM had slightly significant effect on final body weight BW between groups CSM1(FM: CSM; 2:1) and CSM2 (FM:CSM; 2:2),  but had no significantly effect on final BW between groups CSM1(FM: CSM; 2:1) and CSM2 (FM:CSM; 2:2). Weight gain (WG) and specific growth rate (SGR) were significantly higher in fish fed diet containing (FM: CSM 2:1) ratio, but no significant differences in WG, SGR and survival rate (SR) values of groups received the ratios of FM: CSM (2:2 and 1:2). The best feed conversion ratio (FCR), and protein productive value (PPV) were obtained by fish fed containing (FM: CSM= 2:1) followed by (FM: CSM= 2:1). There were no significant differences in protein efficiency ratio (PER). The highest apparent digestibility dry matter (DM) was obtained from fish fed diet containing (FM: CSM= 2:1) followed by (FM: CSM= 2:1), with significant (P>0.005) differences between FM: CSM = 2:1 and 2:2 ratio. The opposite trend was observed in apparent digestibility of protein. Meanwhile, there was no significant differences in apparent digestibility of lipid and energy.