Hybrid groupers become one of the important aquatic animals, but gastric pathogen infection causes losses due to Vibrio sp. infections. Ethyl caffeate (EC), a naturally occurring antioxidant and antibacterial derived from medicinal plant. This study investigated the effects of EC on the immune response, growth performance, as well as the systemic and mucosal immunity following Vibrio parahaemolyticus challenge. The hybrid groupers were fed diets containing EC at the concentrations of 0, 0.1, 0.25, and 0.5 g/kg (control, EC0.1, EC0.25, and EC0.5 groups, respectively). This feeding trial was conducted in three-part separate experiments consist of non-specific immune response, growth performance and challenge test experiment. The result demonstrated that the EC0.25 group had the highest total leukocyte count, phagocytic activity, and respiratory burst (O