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Background: In severe COVID-19 cases, a hypercoagulable state may occur. Antiphospholipid syndrome-related auto-antibodies (APSRAs) contribute to coagulopathy, but their role in COVID-19 remains unclear. We aimed to investigate the prevalence of positive APSRAs and their effect on clinical outcomes in confirmed COVID-19 patients. Materials and Methods: In this cross-sectional study, severe hospitalized COVID-19 cases were enrolled. Demographic and clinical data were obtained from the day of admission. APSRAs including IgG and/or IgM anticardiolipin (aCL) and anti-ß2-glycoprotein1 (anti-ß2GP1) as well as lupus anticoagulant (LAC) were measured. Results: In this study, 54 severe COVID-19 cases with positive RT-PCR and chest CT scans were recruited. Positive APSRAs were found in 7 (12.9%) patients. Positive LAC was a more prevalent marker as compared to other tests (11.1%). The prevalence of positive aCL (IgM or IgG) and anti-ß2 GPI (IgM or IgG) w as 1.8% (in an elderly woman). Lower oxygen saturation was found in the positive APSRAs group as opposed to the negative APSRAs group (70.3±9 vs. 84.8±9.7%). The mortality rate in the positive APSRAs group was significantly higher relative to the negative APSRAs group (83.3% vs. 27.1%; Pvalue: 0.01). Likewise, the mechanical ventilation requirement in the positive group was also higher (50% vs. 27.1%, P-value: 0.28). Conclusion: This study indicated that LAC might be associated with critical cases and high mortality of COVID-19. Nonetheless, the mortality was not related to macrothrombotic incidence. [ABSTRACT FROM AUTHOR]