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Introduction: Red blood cell distribution width (RDW) has been introduced as a predictive factor for mortality in several critical illnesses and infectious diseases. This study aimed to assess the possible relationship between RDW on admission and COVID-19 in-hospital mortality., Method: This cross-sectional study was performed using the Isfahan COVID-19 registry. Adult confirmed cases of COVID-19 admitted to four hospitals affiliated with Isfahan University of Medical Sciences in Iran were included. Age, sex, O2 saturation, RDW on admission, Intensive Care Unit admission, laboratory data, history of comorbidities, and hospital outcome were extracted from the registry. Cox proportional hazard regression was used to study the independent association of RDW with mortality., Results: 4152 patients with the mean age of 61.1 ± 16.97 years were included (56.2% male). 597 (14.4%) cases were admitted to intensive care unit (ICU) and 477 (11.5%) cases died. The mortality rate of patients with normal and elevated RDW was 7.8% and 21.2%, respectively (OR= 3.1, 95%CI: 2.6-3.8), which remained statistically significant after adjusting for age, O2 saturation, comorbidities, and ICU admission (2.03, 95% CI: 1.68-2.44). Moreover, elevated RDW mortality Hazard Ratio in patients who were not admitted to ICU was higher than ICU-admitted patients (3.10, 95% CI: 2.35-4.09 vs. 1.47, 95% CI: 1.15-1.88, respectively)., Conclusion: The results support the presence of an association between elevated RDW and mortality in patients with COVID-19, especially those who were not admitted to ICU. It seems that elevated RDW can be used as a predictor of mortality in COVID-19 cases.