Purpose Red blood cell distribution width (RDW) is closely related to inflammatory-related disease markers. The present study aimed to investigate the association between the red blood cell distribution width (RDW) and post-stroke depression (PSD). Patients and Methods A total of 414 patients with acute ischemic stroke (AIS) admitted to our hospital from June 2018 to July 2021 were consecutively enrolled and received 3 months’ follow-up. According to the 17-item Hamilton Depression Scale (HAMD) assessment, they were divided into PSD group and non-PSD group. Diagnosis of PSD was made in accordance with DSM-IV. RDW was recorded within 24 hours of admission. Results Among the included 414 patients, 95 (22.95%) patients were diagnosed as having PSD at 3 months after stroke. The results showed significantly higher level of RDW in patients with depression (13.69 (IQR13.24–13.88) vs. 13.56 (IQR 12.67–13.77), P<0.001) at admission than patients without depression. After adjustment for potential confounding factors, the odds ratio of PSD was 5.707 (95% CI, 2.717–11.989) for the highest tertile of RDW compared with the lowest tertile. Moreover, based on the receiver operating characteristic (ROC) curve, the optimal cutoff of RDW levels as an indicator for the prediction of PSD was projected as 13.01, which yielded a sensitivity of 83% and a specificity of 41.0%, with an area under the curve (AUC) of 0.643 (95% CI, 0.585–0.701; P = 0.012). Conclusion Higher RDW levels at admission were found to be correlated with PSD 3 months after stroke.
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