Abstract: OBJECTIVE To explore the changes of the levels of serum microribonucleic acid 98-5p (miR-98-5p), endothelial cell specific molecule-1 (ESM-1), soluble thrombomodulin (sTM), and vascular endothelial cadherin (VE-Cad) in patients with sepsis complicated with acute respiratory distress syndrome (ARDS) and their relationship with prognosis was analyzed. METHODS Total of 129 patients with sepsis complicated with ARDS admitted to Haikou Traditional Chinese Medicine Hospital from Sep 2018 to Sep 2022 were recruited, and were divided into the mild group (39 cases), the moderate group (56 cases) and the severe group (34 cases) according to the severity of the disease. After 4 weeks of follow-up, they were divided into the death group (52 cases) and the survival group (77 cases) according to the survival condition. The levels of serum miR-98-5p, ESM-1, sTM and VE-Cad among patients with different levels of severity, and the clinical data between the death group and the survival group were compared. And the risk factors for sepsis with ARDS were analyzed by multivariate Logistic regression analysis. The predictive value of the levels of serum miR-98-5p, ESM-1, sTM and VE-Cad on the prognosis of sepsis patients with ARDS was analyzed by receiver operating characteristic (ROC) curve. RESULTS The level of serum miR-98-5p decreased when the disease was severer, while the levels of serum ESM-1, sTM, and VE-Cad increased with the severity (P＜0.05). Low serum level of miR-98-5p and high levels of ESM-1, sTM and VE-Cad were independent risk factors for death of septic patients with ARDS (P＜0.05). The sensitivity of combined detection of serum miR-98-5p, ESM-1, sTM, and VE-Cad for predicting the prognosis of sepsis complicated with ARDS was 90.38%, with the specificity of 89.61% and the curve of area of 0.953, which showed the highest diagnostic value (P＜0.05). CONCLUSION The levels of serum miR-98-5p, ESM-1, sTM and VE Cad were closely related to the severity of sepsis patients with ARDS. Low expression of serum miR-98-5p and high expression of serum ESM-1, sTM and VE-Cad were independent risk factors for the death of sepsis patients with ARDS. And the combined detection showed great diagnostic value.