BACKGROUND: An increase in high-density lipoprotein (HDL) is well associated with a decreased cardiovascular risk, especially atherosclerosis. Recent studies suggest that lower levels of HDL may also be associated with an increased risk of sepsis and an increased rate of mortality in septic patients. However, this conclusion remains controversial.METHODS: MEDLINE, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019.All studies were conducted to evaluate the correlation of lipoprotein levels and the risk and outcomes of sepsis in adult patients. The primary outcomes were the risk and mortality of sepsis. RESULTS: Seven studies comprising 791 patients were included. Lower levels of HDL had no marked relevance with the risk of sepsis (odds radio [OR] for each 1 mg/dL increase, 0.94; 95％ CI 0.86–1.02; P=0.078), whereas lower HDL levels were related to an increased mortality rate in septic patients (OR for below about median HDL levels, 2.00; 95％ CI 1.23–3.24; P=0.005). CONCLUSION: This meta-analysis did not reveal a significant association between lower HDL levels and an increase in the risk of sepsis, whereas it showed that lower HDL levels are associated with a higher mortality rate in septic adult patients. These findings suggest that HDL may be considered as a promising factor for the prevention and treatment of sepsis in the future.