BackgroundSepsis is the leading cause of death worldwide, and a number of biomarkers have been developed for early mortality risk stratification. Red blood cell distribution width (RDW) is a routinely available hematological data and has been found to be associated with mortality in a number of diseases; therefore, we aim to address the association between RDW and mortality in critically ill patients with sepsis.MethodsWe analyzed data of critically ill adult patients with sepsis on the TriNetX platform, excluding those with hematologic malignancies, thalassemia, and iron deficiency anemia. Propensity score-matching (PSM) (1:1) was used to mitigate confounding effects, and hazard ratio (HR) with 95% confidence (CI) was calculated to determine the association between RDW and 30-day mortality. We further conducted sensitivity analyses through using distinct cut-points of RDW and severities of sepsis.ResultsA total of 256,387 critically ill septic patients were included in the analysis, and 40.0% of them had RDW equal to or higher than 16%. After PSM, we found that high RDW was associated with an increased 30-day mortality rate (HR: 1.887, 95% CI 1.847–1.928). The associations were consistent using distinct cut-points of RDW, with the strength of association using cut-points of 12%, 14%, 16%, 18% and 20% were 2.098, 2.204, 1.887, 1.809 and 1.932, respectively. Furthermore, we found consistent associations among critically ill septic patients with distinct severities, with the association among those with shock, receiving mechanical ventilation, bacteremia and requirement of hemodialysis being 1.731, 1.735, 2.380 and 1.979, respectively.ConclusionWe found that RDW was associated with 30-day mortality in critically ill septic patients, underscoring the potential as a prognostic marker in sepsis. More studies are needed to explore the underlying mechanisms.