There is inconsistent toxicity of nitrite and ammonia nitrogen at different salinities and temperatures. To study the effect of nitrite, ammonia, salinity, temperature stress about Litopenaeus vannamei, this experiment is a four-factor and three-level orthogonal test of 35 days, consisting of nitrite concentration (0.05, 0.5, 5 mg/L), ammonia nitrogen concentration (0.2, 0.9, 4 mg/L), salinity (0.5, 15, 30), temperature (20, 25, 30 ℃). The results showed that with increasing nitrite and ammonia nitrogen concentrations, survival rate and body length daily growth value decreased significantly (P<0.05), serum malondialdehyde (MDA), urea nitrogen (BUN) and blood ammonia (AMM) content increased significantly (P<0.05), and superoxide dismutase (SOD) activity in hepatopancreas increased significantly (P<0.05). With increasing salinity, serum activities of alanine aminotransferase (ALT) and azelaic aminotransferase (AST) were significantly (P<0.05) lower; daily growth values of body length, daily growth values of body weight, SOD and alkaline phosphatase (AKP) activities were significantly (P<0.05) higher. With increasing temperature, survival rate decreased significantly (P<0.05), serum BUN, AMM content and SOD activity increased significantly (P<0.05). The interaction between nitrite and salinity had the greatest effect on survival rate. Salinity had the greatest effect on daily growth values of body length and body weight. Ammonia nitrogen had the greatest effect on MDA content. Nitrite had the greatest effect on BUN and AMM content, as well as SOD activity. The interaction between nitrite and ammonia nitrogen had the greatest effect on ALT, AST, ACP activity. The interaction between nitrite and temperature had the greatest effect on AKP activity. The study showed that both interaction between salinity and nitrite and the interaction between ammonia and nitrite produced synergistic effects of ALT and AST activities, with the toxic effects of nitrite playing a dominant role at low salinity. In the external environment, the antioxidant capacity of the body under co-stress was mainly affected by the contents of nitrite and ammonia nitrogen. The antioxidant capacity was weaker at 20 ℃. About growth and antioxidant function of Litopenaeus vannamei, the interaction between nitrite and ammonia nitrogen, salinity, temperature had a greater effect than single factor. The present study may provide a reliable experimental basis for a healthy and sustainable industry of Litopenaeus vannamei, and the nitrite should be controlled to be lower than 0.5 mg/L, the ammonia nitrogen to be lower than 0.9 mg/L, the water temperature to be lower than 30 ℃ [ABSTRACT FROM AUTHOR]