This study was aimed to address the promising evaluation of Cissus quadrangularis plant (stem) and lipopolysaccharide (LPS from bacteria) supplemented diets on innate immune response in Lates calcarifer fingerlings against Aeromonas hydrophila infection. Fingerlings were fed supplemented diets containing four different concentrations of C. quadrangularis (0.5, 1.0, 1.5 and 2.0 g kg À1 feed), LPS (25, 50, 75 and 100 mg kg À1 feed) and control (normal formulated diet) for 60 days. The fish fingerlings fed supplemented diet displayed significant differences (P < 0.05) in specific growth rate (SGR) and relative percentage survival compared to the control group fed without C. quadrangularis and LPS-supplemented diet. Fingerlings were injected intraperitoneally with 100 lL lethal dose of A. hydrophila containing 1 9 10 6 CFU g À1 . Supplementation of C. quadrangularis and LPS diet significantly increased biochemical profile such as protein, lipid and carbohydrate content, haematological parameters of L. calcarifer fingerlings in different experimental periods when compared with the control group. Dietary doses of C. quadrangularis and LPS-supplemented diet significantly influenced growth performance and increased survival rate in L. calcarifer fingerlings against A. hydrophila infection.