Lipids take part in many pathophysiological processes of sepsis, thus, the variation of lipid composition may have clue on the severity and pathogen to sepsis. The objective of our study is to expand the profile of lipid compositions and screen potential biomarkers in intensive care unit (ICU) patients with sepsis.Patients admitted to the ICU clearly diagnosed with celiac sepsis were included in this prospective study. Age-matched healthy participants from the Physical Examination Center were used as the control group. Blood samples were obtained from patients within the first 12 h of admission. We analysed different components of the lipid metabolism between the sepsis patients and controls and described characteristic features during sepsis.Thirty patients with celiac sepsis and 30 sex- and age-matched healthy controls were enrolled in this study. The lipid metabolic signature was obviously different between the sepsis patients and healthy controls and was mostly downregulated in sepsis patients. We identified 65 lipid species. Sixty-four lipid molecules were found to be significantly downregulated in sepsis patients, and only the level of one phosphatidylethanolamine (PE) molecule, PE (34:2) was higher in the sepsis patients with sepsis group comparing with the control group. The analysis of metabolic pathway illustrated the different lipid molecules were closely related to Phosphatidylcholine (PC), Lysophosphatidylcholine (LPC), and PE.Sepsis contributes to impaired expression of most lipids, which mainly result in the disorder of glycerolipid metabolic pathway, including Phosphatidylcholine (PC), Lysophosphatidylcholine (LPC), and PE.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.