Three isonitrogenous diets containing 60 g kg–1, 90 g kg–1 or 120 g kg–1 lipid were formulated and fed to the Litopenaeus vannamei (2.00 ± 0.08 g) under two salinities (25 or 3 psu) in triplicate for 8 weeks. Shrimp fed 90 g kg–1 lipid had higher weight gain and specific growth rate than shrimp fed the other two diets regardless of salinity, and the hepatosomatic index increased with increasing dietary lipid at both salinities. The shrimp at 3 psu had significantly lower survival and ash content, higher condition factor, weight gain and specific growth rate than the shrimp at 25 psu. Increasing dietary lipid level induced the accumulation of serum MDA regardless of salinity, and at 3 psu, it reduced the serum GOT and GPT activities and the mRNA expression of TNF-α in intestine and gill of L. vannamei. The hepatopancreatic triacylglycerol lipase (TGL) and CPT-1 mRNA expression showed the highest value in shrimp fed 90 g kg–1 lipid diet at 3 psu. This study indicates that 120 g kg–1 dietary lipid may negatively affect the growth and induce oxidative damage in shrimp, but can improve immune defence at low salinity; 60 g kg–1 dietary lipid cannot afford the growth and either has no positive impact on the immunology for L. vannamei at 3 psu.