Epinephelus fuscoguttatus is a new culturing breed with great commercial values and broad market prospects. Frequent invasion of disease restricts the development of E. fuscoguttatus industry. With the characteristics of pollution-free, low-toxic, and low residuals, Chinese herbs as immunostimulants may be candidates for the prevention and control the diseases among E. fuscoguttatus. In this study, Chinese herbal immunostimulants were screened using nitroblue tetrazolium (NBT) reduction method by incubating the isolated white blood cell with water extracts from Chinese herbs. Water extracts from 39 kinds of 100 mg/ml Chinese herbs mixed with or without 5.0 mg/ml zymosan were utilized. Phagocytizing latex beads was employed to determine the effect of water extracts on the respiratory burst activity of the white blood cells on the phagocytic activity. The screened Chinese herbal immunostimulants were mixed with the feedstuff to feed E. fuscoguttatus. The results showed that 10 Chinese herbs extracts significantly increased the respiratory burst of white blood cells more than 15% compared to those in the control group. Three Chinese herbs extracts mixed with zymosan significantly increased the respiratory burst of white blood cells more than 70%. The water extracts from Caulis spatholobi, Cortex phellodendri amurensis and Herba ecliptae prostratae simultaneously elevated the respiratory burst and the phagocytic activity of white blood cell of E. fuscoguttatus. The in vivo experiments also demonstrated that the water extracts from Caulis spatholobi, Cortex phellodendri amurensis and Herba ecliptae prostratae significantly elevated the respiratory burst and the phagocytic activity of white blood cell and head kidney white cells of E. fuscoguttatus. In this study, 3 Chinese herbal immunostimulants were screened, which significantly enhanced the immune responses in E. fuscoguttatus. These results provide evidence to the development and application of new, safe and effective immunostimulants of E. fuscoguttatus.