BackgroundMultiple medications with anti-inflammatory effects have been used to manage the hyper-inflammatory response associated with COVID-19. Aspirin is used widely as a cardioprotective agent due to its antiplatelet and anti-inflammatory properties. Its role in hospitalized COVID-19 patients has been assessed and evaluated in the literature. However, no data regards its role in COVID-19 critically ill patients. Therefore, this study aims to evaluate the use of low-dose aspirin (81-100 mg) and its impact on outcomes in COVID-19 critically ill patients. MethodThis is a multicenter, retrospective cohort study for all adult critically ill patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on aspirin use during ICU stay. The primary outcome is the in-hospital mortality; other outcomes were considered secondary. Propensity score-matched used based on patient’s age, SOFA score, MV status within 24 hours of ICU admission, prone position status, ischemic heart disease (IHD), and stroke as co-existing illness. We considered a P value of < 0.05 statistically significant.ResultsA total of 1033 patients were eligible; 352 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality (HR (95%CI): 0.73 (0.56, 0.97), p-value=0.03) were lower in patients who received aspirin during hospital stay. On the other hand, patients who received aspirin have a higher risk of major bleeding compared to the control group (OR (95%CI): 2.92 (0.91, 9.36), p-value=0.07); but was not statistically significant.ConclusionAspirin use in COVID-19 critically ill patients may have a mortality benefit; nevertheless, it may be linked with an increased risk of significant bleeding. The benefit-risk evaluation for aspirin usage during an ICU stay should be tailored to each patient.