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Purpose: The aim of our study was to evaluate the prevalence of aPLAs among Tunisian critically-ill covid19 and non-covid19 patients and to investigate the clinical significance of aPLAs by determining the SOFA score and their respiratory failure during their ICU stay. Methods: We conducted a prospective observational cohort study including critically ill COVID-19 patients and non-COVID-19 patients with pulmonary origin sepsis, admitted to the intensive care unit. Blood samples were collected on days 1, 3, 5, 8 and 10 of hospitalization in order to measure titers of anti-cardiolipin (aCL), anti-phosphatidylserine (aPS) by chemiluminescence immunoassay. Results: We enrolled 43 COVID-19 patients and 31 non COVID-19 with pulmonary origin sepsis. In-hospital mortality rate was significantly higher (p=0.026) in COVID-19 patients (79%). 58.8% of COVID-19 patients were aPLA positive; however, only 22.5% of the non-COVID-19 were positive for aPLA (p=0.002). A significant positive correlation existed between respiratory SOFA component at days 3, 5, 8 and 10 and anti-phospholipid antibodies concentrations. Conclusion: Based on our results, for the first time, anti-phospholipid antibodies may be used as an independent indicator of respiratory organ failure in critically ill patients, to stratify and assess the prognosis of pulmonary origin sepsis and COVID-19.