The aim of this study was to explore the dynamic changes in characteristic serum metabolic markers and pathways during early sepsis in rats. By using cecal ligation and puncture (CLP), we made rat models of sepsis, which were randomly divided into 5 groups with 10 rats in each group: group A, group B, group C, group D, and group E. We collected 2 mL of arterial blood at 0, 6, 12, 24, and 48 hours from rats in group A-E respectively and isolated serum via centrifugation. Next, adopting metabolomics analysis methods, we screened for metabolites from the animal serum with statistically and biologically significant abundance changes, and used the KEGG database to analyze the respective metabolic pathways. In all, our findings reveal that D-glucosamine 6-phosphate, D-glucosamine phosphate, α-D-glucosamine 1-phosphate, D-glucosamine 1-phosphate, and 5-hydroxy isocyanate decline continuously from 12 hours, while L-phenylalanine, (S) -α-amino-β-phenylpropionic acid, 5-methoxy indole acetic acid salt, 5-methoxy indole acetic acid, goose deoxyglycolic acid salt, goose deoxyglycolic acid, and Chen's deoxygenated sugar alcohol started to decrease from 6 hours. Additionally, 3.2,3-Bis-O-(geranyl geranyl)-sn-glycerol- 1-phosphoric acid-L-serine levels rose continuously from 12 hours. We found 13 differentially regulated ions, primarily ones involved in pathways responsible for the metabolism of sugar, amino acids, and lipids, which are related to the disorder of energy metabolism. Our findings mark serum-derived D-glucosamine and its phosphorous derivatives as characteristic metabolic markers of sepsis in rats. Copyright 2020 Biolife Sas. www.biolifesas.org.