The objective of this study was to evaluate the effects of replacing soybean meal (SBM) with cottonseed meal (CSM) on the growth performance, feed utilization and hematological parameters of male Nile tilapia fingerlings. Five isonitrogenous diets (containing 31.82% crude protein) containing graded levels of CSM to replace SBM protein was fed to triplicate groups of fish. The diets were supplemented with lysine so that they were similar to the control diet. The results of the 14-week feeding experiment indicated that up to 75% of SBM could be replaced by CSM without causing a significant reduction in growth. Fish fed the diet highest in CSM had a significantly lower protein efficiency ratio and a significantly higher feed conversion ratio than fish fed the other diets. High survival was observed in all the dietary treatments, and no significant difference was observed among treatments. The apparent digestibility coefficients of dry matter and phosphorus decreased significantly with an increase in the dietary CSM level, whereas the apparent digestibility of lipid was not affected by the dietary treatment. Significant differences were found in the hemoglobin, haematocrit, red blood cell and white blood cell contents in fish fed diets with different CSM levels. These findings suggest that up to 41.25% CSM can be used to replace 75% of SBM protein in diets for male Nile tilapia fingerlings without any adverse effects on the growth performance, feed utilization, body composition and hematological indexes provided the CSM diets are supplemented with lysine.