The objective of this study was to evaluate the effect of digestible Protein to Energy ratio (P/E) on growth performance, body composition and enzymatic digestive activity of juvenile tilapia (Oreochromis niloticus x O. mossambicus) reared in seawater. Six diets were evaluated (30, 23, 20, 15, 10 and 8 P/E) on the growth, digestibility, body composition and enzymatic digestive activity of juvenile tilapia. The results indicated that the P/E ratios in diets, significantly affects the growth, survival, Feed Conversion Ratio (FCR), lipid content in the body and enzymatic digestive activity. Maximum body weight was recorded in the treatments with P/E ratios of 30, 23 and 20 (20.6, 23.7 and 25.7 g, respectively) and minimum body weight (5.9 g) was recorded with P/E ratio of 8. The FCR increased significantly in P/E levels of 15, 10 and 8 mg/kJ. In conclusion, the best P/E ratio to culture juvenile tilapia in seawater was estimated in 27 mg/kJ.