Abstract: UHPLC-QTOF-MS was applied to non-targeted metabolomics study of mice infected with K. pneumoniae ATCC^® BAA 2146 to discover potential biomarkers and metabolic pathways that are associated with sepsis. Fifty-eight metabolites were identified by principal components analysis (PCA) and partial least-squares discriminant analysis (OPLS-DA), which was combined with variable projection importance (VIP) and nonparametric test. Eighteen of the 58 metabolites were further found to be involved in 8 metabolic pathways, including nicotinate and nicotinamide metabolism, pyrimidine metabolism, vitamin B6 metabolism, taurine and hypotaurine metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism and glycerophospholipid metabolism.