The suitability of tuna by-product meal (TBM) as a replacement for fish meal (FM) in the diet of juvenile greater amberjack Seriola dumerili was investigated for its effect on growth, mercury (Hg) levels in the fish body, phosphorus (P) load, and plasma chemistry. FM was the main protein source in the control diet (C), and it was replaced by TBM at 25%, 50%, 75%, and 100% to formulate diets TM25, TM50, TM75, and TM100, respectively. The experiment was performed in triplicate, stocking 30 juveniles (mean weight: approximately 6.7 g) in each 500 L tank. After a 42 d rearing period, there were no significant differences in growth, nutrient digestibility, or productive value between diets C and TM25. However, a quadratic polynomial regression analysis suggested that the optimal dietary level of TBM against final weight was 14.5%. A significant linear correlation was observed between Hg in the diet and fish whole body, but the level was far lower, posing health risks to humans. Owing to the lower P intake of fish fed with the TBM-based diets, their P load was significantly reduced compared to the control group. Plasma levels of total protein, total cholesterol, and albumin in the TM75 and TM100 groups were significantly lower than those in the C, TM25, and TM50 groups. These results suggest that 14.5% of FM protein can be replaced by TBM protein in the diet of juvenile greater amberjack and that a significant reduction in P load can be achieved with a TBM-based diet.