We evaluated the effect of stocking density on the concentrations of oxy-hemocyanin and lactate in hemolymph, the antioxidant ability of the hepatopancreas, and the biochemical composition in large and small individuals of the prawn Macrobrachium nipponense (de Haan, 1849) cultured in a cage system. Juveniles (0.24 g initial weight) were stocked in 15 cages with stocking densities of 40, 80, 120, 160, and 200 individuals/m2 for 8 weeks. The results demonstrated that final mean weight, weight gain, gross feed conversion ratio, and survival rate were significantly lower in stocking densities of 160 and 200 individuals/m2 (P<0.05) than in other treatment groups, not through water quality deterioration or food competition, but through the role of density as an environmental stress factor. The coefficient of variation (CV) of body weight increased as the stocking density increased, and the CV in the 160 and 200 individuals/m2 groups were over 70%. The values of hemolymph oxy-hemocyanin and lactate concentration, superoxide dismutase (SOD), catalase (CAT) activities, malondialdehyde (MDA) content, and heat-shock protein 70 (HSP70) mRNA expressions of hepatopancreas in small individuals were significantly higher than those of the large ones in high stocking densities of 160 and 200 individuals/m2. This study provides evidence that crowding stress can stimulate the physiological response of the small individuals raising their oxy-hemocyanin and lactate level in the hemolymph and decreasing antioxidant ability on hepatopancreas, which ultimately lead to suppress growth performance of the small individuals.