ObjectiveThis study aimed to investigate the predictive value of microRNA‐146b (miR‐146b) on acute respiratory distress syndrome (ARDS) risk, and the correlation of miR‐146b with disease severity and 28‐day mortality in sepsis patients.MethodsA total of 104 sepsis patients and 100 healthy controls (HCs) were consecutively enrolled, and miR‐146b relative expression in their plasma samples was detected by reverse transcription‐quantitative polymerase chain reaction. In sepsis patients, disease severity was assessed using Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score. ARDS occurrence and 28‐day mortality were recorded.ResultsMiR‐146b was decreased in sepsis patients compared to HCs. ARDS occurred in 30 (28.8%) sepsis patients, and miR‐146b was reduced in ARDS sepsis patients compared to non‐ARDS sepsis patients. Meanwhile, miR‐146b distinguished ARDS sepsis patients from non‐ARDS sepsis patients (area under the curve (AUC): 0.728, 95% confidence interval (CI): 0.627‐0.829). Subsequent multivariate logistic regression showed that miR‐146b, age, smoke, respiratory infection, and serum creatinine predicted ARDS risk independently, and their combination well‐discriminated ARDS sepsis patients from non‐ARDS sepsis patients (AUC: 0.863, 95% CI: 0.792‐0.934). Additionally, miR‐146b was negatively correlated with serum creatinine, white blood cell, C‐reactive protein, APACHE II score, and SOFA score, while positively correlated with albumin. Regarding prognosis, miR‐146b was decreased in 28‐day sepsis deaths compared to 28‐day sepsis survivors, and it discriminated 28‐day sepsis deaths from 28‐day sepsis survivors (AUC: 0.785, 95% CI: 0.680‐0.890).ConclusionMiR‐146b might serve as a potential biomarker for ARDS prevention and prognostic reflection in sepsis.