Saline-alkaline waters in China are widely distributed and are of various types, primarily carbonate and sulfate. Due to the high alkalinity of saline-alkaline waters, only a few low saline-alkaline waters can be used for freshwater fish farming. However, the area of saline-alkaline waters in China has been increasing annualy; therefore, an urgent need to take measures for the ecological treatment of soil salinization, exists. Litopenaeus vannamei has been widely chosen as a research object in recent years owing to its advantages, such as fast growth and strong environmental adaptability and research has been conducted on its tolerance to carbonate alkalinity. However, research lacks on the impact of sulfate-type water on Litopenaeus vannamei. Therefore, the present experiment was designed to investigate the effects of SO₄²⁻, a key saline ion in sulfate-type waters, on histological structure, immunity, antioxidant capacity, and ion transport capacity of Litopenaeus vannamei. First, the 96 h LC₅₀ of sulfate on Litopenaeus vannamei was determined to be 54.71 mmol/L by LC₅₀ experiment. Further, a control group (10 mmol/L SO₄²⁻) and an experimental group (60 mmol/L SO₄²⁻) were established and exposed for 96 h. At 0, 24, 48, 72, and 96 h of exposure, the shrimp hepatopancreas and gills were collected for pathological studies. At 0, 6, 12, 24, 48, 72, and 96 h of exposure, the hepatopancreas and gill tissues of Litopenaeus vannamei were collected for the determination of physiological indicators (ACP, AKP, SOD, GPX, CAT, MDA, NKA, and NHE). The results showed that: (1) The degree of damage to the hepatopancreas and gill of Litopenaeus vannamei increased gradually with the increase of stress time; (2) The activity of immunoenzymes (ACP and AKP) in hepatopancreas and AKP in gill showed an overall trend of “increase-decrease-increase-decrease-increase” with the increase of stress time; the activity of ACP in gill showed an overall trend of “increase-decrease-increase”; (3) With the increase of stress time, SOD, GPX and CAT in hepatopancreas showed an overall trend of “increase-decrease- increase-decrease” and the MDA content first increased and then decreased. In gill, SOD activity and MDA content showed the “increase-decrease-increase” trend, CAT activity showed the “decrease-incerase-decrease” trend, and GPX activity showed the “decrease-increase-decrease-increase” trend; (4) the activities of ion transporting enzymes (NKA and NHE) in gill showed the trends of “increase-decrease-increase” and “decrease-increase-decrease-increase” respectively, with the increase of stress time. These results indicate that Litopenaeus vannamei has a certain tolerance to sulfate and can adapt to the sulfate environment by regulating its own immune, antioxidant, and ion transport capacities. However, prolonged exposure would exceed the regulatory range of these physiological functions and cause severe damage to the hepatopancreas and gills of Litopenaeus vannamei, affecting its normal functions and eventually leading to mortality.