For a study, researchers sought to identify and analyze determinants of oxygenation over time in patients with COVID-19 acute respiratory distress syndrome (ARDS) using Berlin definition categories. A prospective cohort study of mechanically ventilated patients admitted with ARDS between 3/20/2020 and 10/31/2020. On days 1, 3, and 7, epidemiological and clinical data on admission, outcomes, ventilation, respiratory mechanics, and oxygenation variables were collected for the entire population and ARDS categories. About 1,525 patients, aged 61±13, 69% of whom were male, met ARDS criteria; the most common comorbidities were obesity, hypertension, diabetes, and respiratory disease. On admission, 331 (21%), 849 (56%), and 345 (23%), respectively, had mild, moderate, and severe ARDS; all received lung-protective ventilation (mean tidal volumes between 6.3 and 6.7 mL/kg PBW) and intermediate PEEP levels (10–11 cmH2O). PaO2/FiO2, plateau pressure, static compliance, driving pressure, ventilation ratio, pH, and D-dimer of more than 2 mg/L remained significantly different among the ARDS categories over time. In-hospital mortality was 55%, 58%, and 70%, respectively (P<0.000). BMI, preexisting respiratory disease, D-dimer of more than 2 mg/L, day 1-PEEP, and day 1-ventilatory ratio were independent predictors of changes in PaO2/FiO2 over time. Hypoxemia in COVID-19-related ARDS patients was related to comorbidities, dead space and activated coagulation markers, and disease severity, as measured by the PEEP level required.