Abstract: OBJECTIVE To analyze the role of serum endothelial cell-specific molecule-1 (ESM-1) and soluble thrombomodulin (sTM) expression levels in early identification and prognostic prediction for patients with sepsis-related acute respiratory distress syndrome (ARDS). METHODS A total of 90 patients with sepsis-related ARDS (combined ARDS group), 45 sepsis patients without ARDS (sepsis group) and 45 healthy individuals (normal control group) admitted to Xi'an No. 1 Hospital were selected. The serum ESM-1 and sTM expression levels were compared among the combined ARDS group, sepsis group and normal control group. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of serum ESM-1, sTM and their combination for sepsis-related ARDS, as well as their predictive value for 28-day mortality. RESULTS There were significant differences in serum ESM-1 and sTM levels among the normal control group, sepsis group and combined ARDS group (P＜0.05), with higher levels in the combined ARDS group(10.36±1.45) ng/ml and (126.33±21.56) μg/L. ROC curve analysis showed that the area under the curve (AUC) (95%CI) for the diagnosis of sepsis-related ARDS by serum ESM-1, sTM and their combination were 0.793 (0.754-0.845), 0.781 (0.738-0.820) and 0.875 (0.839-0.905), respectively. The AUC (95%CI) for predicting sepsis-related ARDS mortality were 0.807 (0.766-0.844), 0.825 (0.785-0.860) and 0.893 (0.859-0.921), respectively. CONCLUSIONS The serum ESM-1 and sTM levels are abnormally elevated in patients with sepsis-related ARDS, and the combined application of ESM-1 and sTM can serve as a basis for early identification of sepsis-related ARDS patients and also have a certain predictive effect on the prognosis of sepsis-related ARDS patients.