Increased soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) levels have been reported in patients with sepsis. We tested the hypotheses that serum sTREM-1 levels increase in the early phase of sepsis and decrease after sepsis under appropriate treatment and that sTREM-1 levels can predict therapeutic outcomes. One hundred and fifty-five patients prospectively underwent blood samples including biochemical data, sTREM-1, and biomarkers on endothelial dysfunction as well as clinical severity index examinations. Blood samples from Days 1, 4, and 7 after admission were checked. For comparison, 50 healthy subjects were selected as healthy control. Those patients who had sepsis had significantly higher sTREM-1 levels than those of healthy control. sTREM-1 levels positively correlated with biomarkers for endothelial dysfunction (ICAM-1, VCAM-1, and E-selectin) and lactate level as well as clinical severity index (maximum 24 h APACHE score and Sequential Organ Failure Assessment (SOFA) score) upon admission. sTREM-1 concentrations were significantly higher from Day 1 to Day 7 in the non-survivors than in the survivors. A stepwise logistic regression analysis showed only sTREM-1 level and maximum 24 h SOFA score upon admission were significantly associated with fatality. Area under the receiver operating characteristic curve analysis for the diagnostic accuracy of sTREM-1 in sepsis-related fatality gave a value of 0.726, with a cutoff value of 384.6 pg/mL (sensitivity = 80.8% and specificity = 61.5%). sTREM-1 level may be valuable in auxiliary diagnosis, and it can serve as a useful biomarker as a screening service and follow-up therapeutic outcomes in sepsis.