Two trials were conducted to evaluate the efficacy of commercial enzyme-treated soy (ESBM) to replace the use of fish meal (FM) in practical diets for Florida pompano Trachinotus carolinus. The reference diet which has been run in numerous trials for Florida pompano was formulated using 150, 466 and 80 g kg-1 of FM, soybean meal (SBM) and corn protein concentrate (CPC), respectively. In trial 1, test diets were produced by replacing FM with 30.8, 61.4 and 92.1 g kg-1 of ESBM. In trial 2, test diets were produced by replacing FM with 28.9, 89.8, 120.1 g kg-1 of ESBM. Triplicate group of fish in trial 1 (mean weight = 13.05 ± 0.34 g) and trial 2 (mean weight = 18.45 ± 0.49 g) were fed these diets to apparent satiety for eight weeks. Growth performance was affected as the dietary FM was replaced with ESBM. In trial 1, final weight (FW), percentage weight gain (PWG) and thermal growth coefficient (TGC) were lower in 6 g kg-1 of FM compared to 15 g kg-1, while feed conversion ratio (FCR) significantly higher in fish fed the lowest inclusion level of FM (6 g kg-1). In trial 2, FW was significantly lower when FM completely replaced by ESBM and no significant differences in other growth parameters. In all trials, no significant differences were observed in terms of crude protein, moisture, fat, crude fiber, dry matter and ash content of the fish. No significant differences in serum levels of total protein, albumin, alkaline phosphatase, alanine transaminase, aspartate transaminase, glucose and bile acids were observed in either trial. However, in trial 1, serum cholesterol level was higher in fish fed 150g kg-1 FM compared to other dietary treatments. The histomorphological structure of liver and distal intestine were slightly affected by lower inclusion level of FM. Overall, there was a decreasing trend in pompano growth performance as the inclusion of FM decreased. All parameters indicated that ESBM could be used to reduce the inclusion of FM from 150 to 90 g kg-1.