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Background: Oxidative stress plays a critical role on the processes of sepsis, and several microRNAs have been identified that may regulate the occurrence of oxidative stress. However, the relation between oxidative stress-related microRNA 27a (miR-27a) and sepsis is unknown. The present study aimed to determine the value of circulating miR-27a for the diagnosis and prognosis of sepsis., Methods: This retrospective study included 23 patients with sepsis and 25 without sepsis treated at the emergency intensive care unit (EICU) or our institution between January 2019 and January 2020. Levels of circulating miR-27a and levels of oxidative stress-related indicators were measured and compared between sepsis and non-sepsis patients. Receiver operating characteristic (ROC) curve analysis was used to determine diagnostic efficiency of miR-27a., Results: Circulating miR-27a levels in sepsis patients were higher than those in non-sepsis patients (p < 0.05), and levels were significantly higher in patients that died than those that lived (p < 0.05). In patients with sepsis, circulating miR-27a level was positively correlated with serum malondialdehyde (MDA) level (rs = 0.529, p = 0.007), and negatively correlated with serum glutathione peroxidase (GSH-Px) level (rs = - 0.477, p = 0.016). No significant correlation was observed between circulating miR-27a and serum superoxide dismutase (SOD) in sepsis patients (rs = - 0.340, p = 0.096). The area under the ROC curve (AUC) of miR-27a level for prediction of sepsis was 0.717 (p = 0.009) and for 28-day mortality was 0.739 (p = 0.003)., Conclusions: This study showed that circulating miR-27a level is correlated with oxidative stress and mortality in patients with sepsis, and may serve as a potential non-invasive molecular biomarker., (© 2022. The Author(s).)