Background: Schisandra chinensis is a traditional Chinese herbal medicine which protects hepatic function. Its primary component is polysaccharides which is used in the treatment of hepatic injury, but the mechanism of action of S. chinensis polysaccharides (SCP) in immunological liver injury induced by concavalin A (Con A) is still not clear. Aim: In this study, we aimed to evaluate the hepatoprotective mechanism of SCP in immunological liver injury. Subjects and Methods: In this study, we performed rapid-resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry-based serum metabolomics approach to investigate the hepatoprotective effects of SCP against Con A-induced immunological liver injury in mice. Results: According to our results, SCP significantly increased the activity of superoxide dismutase in the liver; decreased the level of serum aspartate aminotransaminase (AST), serum alanine aminotransaminase (ALT), tumor necrosis factor-α, interferon-γ, interleukin (IL)-1 β, and IL-6 in the serum, and decreased the level of malondialdehyde and nitric oxide in the liver of mice with immunological liver injury induced by Con A. In this study, we identified 17 biomarkers through metabolomic analysis, and after the administration of SCP, 16 of them were found to return to the normal levels. Our analysis suggested that some metabolic pathways are involved in the mechanisms of action of SCP for the treatment of the immunological liver injury, including energy metabolism, amino acid metabolism, taurine metabolism, amino saccharide and nucleotide metabolism, arachidonic acid metabolism, and lipid metabolism. Conclusion: SCP could alleviate the oxidative stress and inflammatory reaction in the immunological liver injury and recover the metabolic dysfunction caused by Con A.