OBJECTIVE : GPR18, a G protein-coupled receptor (GPCR), is involved in bacterial clearance and survival in microbial sepsis. In this study, we examine GPR18 expression on polymorphonuclear neutrophils (PMNs) of patients with sepsis and to determine the potential association with disease severity and outcomes. METHODS : We enrolled 81 patients admitted at the intensive care unit (ICU) with the diagnosis of sepsis. PMNs GPR18 expression was measured by flow cytometry at admission. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHEII) as well as other biomarker were measured at admission. Cox regression analysis was used to determine the influence of PMNs GPR18 expression on 28-day mortality. RESULTS : Patients with sepsis had a decreased percentage of PMNs bearing GPR18 in comparison with healthy subjects (P < 0.001). Compared with survivors, non-survivors had lower percentage of GPR18-positive PMNs, but higher SOFA, APACHEIIscores, and WBC count. There were inverse correlations between the percentage of GPR18-positive PMNs and APACHEII, SOFA score and C-recreative protein (CRP). Using Kaplan-Meier analysis, high percentage of PMNs expressing GPR18 (≥43.7%) was associated with a preferable 28-day survival (P = 0.004). High percentage of PMNs expressing GPR18 (≥43.7%) was significantly and independently associated with 28-day mortality, with a hazard ratio of 0.36 (P = 0.37). Moreover, LPS-Toll-like receptor (TLR)4 signaling mediated the GPR18 expression on PMNs. CONCLUSIONS : These results indicate that decreased percentage GPR18-positive PMNs is associated with increased severity and poorer outcome of sepsis.