Litopenaeus vannamei is native to South Pacific coastal waters and is considered as one of the important euryhaline aquaculture shrimps across the world. Because of its high disease resistance, fast growth, suitability for high-density culture, and other excellent biological characteristics, L. vannamei has become one of the three most important aquaculture shrimps that have the greatest development potential around the world. Salinity is one of the most important and changeable water quality factors affecting the physiology of aquatic organisms. Salinity variation may cause a variety of physiological responses, such as enhancement of stress-related hormones in plasma, stimulation of energy metabolism, and disruption of electrolyte equilibrium. Consequently, marine organisms have developed various survival mechanisms against salinity variation. For example, crustaceans adjust their osmolarity and maintain a stable intra-corporal state by varying related enzyme activities. The immune-enzyme activities of crustaceans are indicative of the fact that the body plays important roles in disease resistance and health maintenance. In addition, digestive enzyme activities directly reflect the ability of the body to digest and absorb nutrients, which affects body survival and growth. However, few studies have reported on the influence of high salinity on the immune and digestive indices of L. vannamei. There are many high-salinity waters in the coastal or northwest regions of China, which can be developed for L. vannamei culture. Through analyzing the effects of high-salt stress on the activities of digestive and immune-related enzymes in L. vannamei, we can enhance our understanding of shrimp stress biology, and provide a theoretical reference for future cultivation of shrimps in high-salt environments. Digestive and immunity-related enzymes of L. vannamei (7.84±0.68) cm were investigated when shrimp were separately exposed to 30, 40, 50, and 60 psu conditions. Shrimp stocking density was 333 ind./m³, with three replicates per treatment, and the experiment lasted for 30 days. The activity of immunity-related enzymes, including superoxide dismutase (SOD), catalase (CAT), alkaline phosphate (AKP), and acidic phosphate (ACP), and digestive enzymes (pepsin, lipase, and amylase) in different tissues (hemolymph, muscle, and hepatopancreas) were investigated. The results showed that salinity significantly influenced the activity of pepsin, lipase, and amylase in the hepatopancreas, with enzyme activity decreasing with an increase in salinity. In the hemolymph, ACP, CAT, and SOD activities showed an "increase-decrease" change trend, whereas AKP increased with an increase in salinity. In muscle tissue, AKP, CAT, and SOD activities showed an "increase-decrease" change trend. In the hepatopancreas, there were no obvious changes in the activities of AKP and ACP, whereas SOD activity decreased significantly when salinity was greater than 40 psu. Our results indicate that high salinity can affect the activities of digestive and immunity-related enzymes in different tissues, particularly under high-salinity conditions (above 50 psu).