Frequent typhoons bring large amounts of precipitation, causing drastic changes in water salinity and stress to aquatic animals. The large number of free radicals generated by stress may lead to aquatic animal mortality, which causes huge economic losses. Although Pacific white shrimp, Litopenaeus vannamei is tolerant to salinities of 1 to 50, drastic salinity changes may be detrimental to their health status. As a new type of protein, yeast-like substances contain a variety of functional substances and nutrients such as nucleic acids, small peptides, oligosaccharides, free amino acids, and rich B vitamins, which can improve the growth performance and health of animals, for example Epinephelus coioides, Scophthalmus maximus, Penaeus monodon. Previous studies have shown that the addition of yeast hydrolysate to feed can improve the non-specific immunity, the diversity of intestinal flora, the digestive enzyme activity, and the ability to utilize sugars and lipids in L. vannamei. It is interesting that yeast-like substances seem to play an active role in the immunoregulation response of aquatic animals to environmental stresses. This study aimed to investigate the effect of yeast hydrolysate addition to feed on the non-specific immune and antioxidant capacity of L. vannamei under salinity stress conditions.Shrimps [initial weight (15.82 ±0.08) g] were randomly divided into 2 groups. The control group was fed with basic feed (Y0), and the experimental group was fed with experimental feed (Y3) supplemented with 3% yeast hydrolysate. After 15 days of culture, they were transferred to the water of salinity 4 (S4) and salinity 28 (S28) for low salinity stress with 3 replicates tanks of each group and 30 individuals in each tank. Groups were named Y0S4, Y0S28, Y3S4, Y3S28 according to different combinations of feed and salinity conditions. The results showed that there was no significant difference in the survival rate of the groups after transferring the shrimp to water with salinities of 4 and 28. The addition of yeast hydrolysate to the feed had no significant effect on serum phenoloxidase (PO) and total nitric oxide synthase (TNOS) activities in L. vannamei. At 1.0 h of low salinity stress, PO and TNOS activities were significantly higher in the Y3S4 group than in the Y0S4 group. The salinity factor had a significant effect on PO and TNOS activities, PO, TNOS activities were significantly higher in the S28 group than in the S4 group at 1.0 h. What’s more, the addition of 3% yeast hydrolysate to the feed significantly increased the hepatopancreas superoxide dismutase (SOD) activity of the shrimps. The studies have shown that the addition of yeast hydrolysate to the feed can increase the hepatopancreas SOD activity of L. vannamei and improve the antioxidant capacity of the shrimp. In the event of low salinity stress, the shrimp can quickly restore the PO and TNOS activities to normal levels, thus improving the resistance of L. vannamei to adverse environments.