Xuebijing (XBJ) injection, a Chinese traditional medicine injection, is widely used in the treatment of sepsis in China, and shows a promising clinical therapeutic effect. However, its impacts on the metabolic changes of sepsis have not yet been reported. We established a septic rat model using cecal ligation and puncture (CLP) and treated with XBJ or placebo (saline). The survival rates were monitored for 7d, the effects of XBJ on liver and kidney tissue morphology, serum biochemistry [alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr)] and cytokines [tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6)] production were assessed. Plasma samples were profiled by gas chromatography/mass spectrometer (GC/MS) and analyzed to evaluate the metabolites changes. We found that XBJ can increase the survival rate of septic rats by reducing multi-organ dysfunctions shown as decrease in serum biochemistry indicators, cytokines, and morphologic changes. A Partial Least-Squares Discriminant Analysis (PLS-DA) score plot indicated that rats undergo significant metabolic changes between the three groups. 21 distinct metabolites with VIP>1.5 and p<0.05 were were identified between these group. These metabolites primarily reflected disorders in energy metabolism, glucose metabolism and amino acid metabolism. This study established the foundation for further research of the mechanisms and therapeutic targets of sepsis.