Mulberry leaf, as a commercially important woody plant medicine or food in China, has been used as feed additive on livestock and poultry due to its excellent pharmacological, security and high value in economy. The present working hypothesis is that dietary mulberry leaf addition will also benefit to fish with its wide-spectrum virtues. To this end, a feeding experiment was conducted to evaluate the role of mulberry leaf along with multi-enzyme premix in golden pompano. Each of five diets with mulberry leaf at dietary levels of 0.0%, 2.0%, 4.0%, 6.0% and 8.0% (D0.0, D2.0, D4.0, D6.0 and D8.0) was fed to fish with initial body weight of 9.02 g in triplicate marine cages for 8 weeks. The results showed that mulberry leaf in all levels along with multi-enzyme premix increased the growth of fish and the growth in D6.0 significantly better than that of D0.0 (P < 0.05). Lipid contents of whole body were evidently increased when the dietary mulberry leaf levels were less than 6.0% (P < 0.05), while in contrast those of muscle were basically decreased. Furthermore, dietary mulberry leaf along with multi-enzyme premix significantly increased serum total protein and high- density lipoprotein and significantly decreased total triglyceride as well as glutamic oxaloacetate transaminase in D6.0(P < 0.05). In addition, mulberry leaf along with multi-enzyme premix significantly increased lipase of stomach in D8.0 compared to that of D0.0 (P < 0.05), and increased lipase of hepatopancreas and trypsin of intestine in all mulberry groups (P < 0.05). Finally, mulberry leaf along with multi-enzyme premix significantly improved the immune response and disease resistance to Vibrio harveyi in all groups (P < 0.05) and the survival rate in D4.0 was the highest. In conclusion, this study presented positive effects of mulberry leaf along with multi-enzyme premix on growth, digestion, lipid metabolism and disease resistance and the recommended addition level of dietary mulberry leaf in formulated feed of juvenile golden pompano is between 4% and 6% in present experimental condition.