This study evaluated the effect of replacing fish meal (FM) with concentrated trout viscera protein hydrolysate (VTPH) on the immune response in juvenile red tilapia (Oreocheromis spp). Five isoenergetic and isoproteic experimental diets were prepared by substituting FM with VTPH at different substitution ratios: 0% (control, D1) 25% (D2), 50% (D3), 75% (D4) and 100% (D5). A total of 180 red tilapia were distributed in 15 tanks. Fish from 3 tanks were fed daily at 2% of the biomass for 25 days with one of the 5 diets mentioned above. At the end of the trial, skin mucus and serum samples were obtained to study different parameters related to humoral immunity. The results indicate that fish fed diets D2 and D3 had significantly higher serum protein values. Also, fish fed the D2 or D5 diets had higher lysozyme activity and fish fed the 100% diet also had significantly higher total immunoglobulin levels than fish fed the control diet. In mucus, fish fed the D2 or D4 diets showed significantly higher mucus protein levels than control fish. However, anti-protease and bactericidal activity decreased in fish fed the D5 or D4 diets, respectively. These results demonstrate that the D2 and D3 diets positively modulate the immune response of juvenile red tilapia compared to that of fish fed the control diet.