The present study explored the dietary administration effects of guanosine monophosphate (GMP) on growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream, Pagrus major. A semi-purified basal diet supplemented with 0% (Control), 0.1% (GMP-0.1), 0.2% (GMP-0.2), 0.4% (GMP-0.4) and 0.8% (GMP-0.8) purified GMP to formulate five experimental diets. Each diet was randomly allocated to triplicate groups of fish (mean initial weight 3.4 g) for 56 days. The obtained results clearly indicated that, growth performance of red sea bream enhanced by dietary GMP supplementation compared to control and significantly higher final weight was found in fish fed diet group GMP-0.4. Specific growth rate (SGR) and percent weight gain (%WG) also significantly higher in diet group GMP-0.4 in compared to control and it was not differed (P > 0.05) with diet group GMP-0.8. Feed intake significantly increased with the supplementation of GMP. Feed conversion efficiency (FCE) and protein efficiency ratio (PER) also improved (P < 0.05) when fish fed the diets containing GMP and diet group GMP-0.4 showed the significantly higher value in compared to control. The Apparent digestibility coefficients (dry matter, protein and lipid) also improved by GMP supplementation and the significantly higher protein digestibility was observed in fish fed diet groups GMP-0.2, GMP-0.4 and GMP-0.8. Among the measured non specific immune parameters peroxidase activity (PA), respiratory burst activity (NBT), Bactericidal activity (BA) were significantly affected by dietary supplementation and highest value obtained in diet group GMP-0.4. Total serum protein, lysozyme activity (LA), and agglutination antibody titer also increased (P > 0.05) by GMP supplementation. In contrast, catalase activity decreased with GMP supplementation. In terms of oxidative stress GMP-0.2 showed best condition with low oxidative stress and high antioxidant level. Moreover, the fish fed GMP supplemented diets had better improvement (P < 0.05) in body protein contents, hepatosomatic index, hematocrit content and glutamyl oxaloacetic transaminase (GOT) and glutamic-pyruvate transaminase (GPT) level than the control group. Supplementation also improved (P < 0.05) freshwater stress resistances. Quadratic regression analysis of WG and LA revealed that, the optimal levels of dietary GMP were 0.45 and 0.48%, respectively, for juvenile red sea bream, which is also in line with the most of the growth performance and health parameters of the fish.