Determining optimum stocking density of the white shrimp Litopenaeus vannamei (Boone) is a big concern for shrimp farmers. However, few studies have assessed the influence of stocking density on the antioxidant status, immunology, digestive enzyme activities, and growth performance of white shrimp in biofloc systems. In this study, these parameters of white shrimp in a biofloc system were compared at three stocking densities: 300 orgs m−3 as low stocking density (LD), 400 orgs m−3 as medium stocking density (MD), and 500 orgs m−3 as high stocking density (HD). The feed conversion ratio in the LD group was significantly lower than that in the MD and HD groups (P < 0.05), and the ultimate individual weight in the LD group was significantly higher than that in the other two groups (P < 0.05). The antioxidant status and immunology parameters, including complement 3, complement 4, lysozyme, superoxide dismutase, glutathione peroxidase and malondialdehyde were all depressed in the HD groups. Furthermore, activities of the digestive enzymes, amylase, trypsin, and lipase were lower in the MD and HD groups than that in the LD group. The highest relative percentage survival was observed in the LD group 10 days after challenge with the pathogen Vibrio harveyi. Results of this study indicated that the immune status and welfare of white shrimp can be seriously impaired in the HD condition (i.e., ≥500 m−3) in biofloc systems. These findings can be used to determine suitable stocking densities in the white shrimp farming industry using the biofloc system.