Background: Oxygenation index [OI = (MAP × FiO₂ × 100)/PaO₂] assesses the severity of hypoxic respiratory failure. Oxygen saturation index [OSI = (MAP × FiO₂ × 100)/SpO₂] is a noninvasive method to assesses the severity of hypoxic respiratory failure. Conventionally used PaO₂/FiO₂ (P/F) ratio to measure the severity of ARDS requires arterial blood gas (ABG) sampling. It tenders limited prognostic information mandating the need for better markers. Oxygenation index (needs arterial sampling) and OSI (a noninvasive method) are substitutes to provide mortality information in ARDS patients. We evaluated the correlation between P/F, OI, and OSI in invasively ventilated COVID-19 ARDS patients (C-ARDS) and looked at its relationship with mortality. Patients and methods: A retrospective study of invasively ventilated C-ARDS >18 years of age managed in COVID ICU. Ventilator settings (FiO₂, mean airway pressure), pulse oximetry (SpO₂), and ABG values (PaO₂) were simultaneously noted at the time of sample collection. Patient outcomes (alive and deceased) were documented. Differences in parameters between survivors and nonsurvivors were assessed using independent sample t-test. Receiver operating characteristic (ROC) analysis with Youden's index was used to identify cutoff values to determine survival. Results: A total of 1557 measurements for 203 patients were collected over the maximum duration of 21 days after ventilation. About 147 (72.4%) were males and 56 (27.6%) were females. On day one of ventilation, 161 (79.3%) had P/F ratio <200, 28 (13.8%) had P/F ratio between 200 and 300, and 14 (6.9%) had P/F ratio >300. There was a linear relationship between P/F ratio and OSI (r = –0.671), P/F and OI (r = –0.753), and OSI and OI (r = 0.893) (p < 0.001). After natural log transform, the correlation between these factors became stronger [P/F ratio and OSI (r = –0.797), PF and OI (r = –0.949), and OSI and OI (r = 0.902) (p < 0.001)]. About 74 (36.5%) patients survived. Survivors had significantly higher P/F ratio as compared with nonsurvivors (p < 0.05). Oxygen saturation index and OI were significantly lower in survivors as compared with nonsurvivors. Based on day-1 reading, a higher OSI (AUC = 0.719, 95% CI = 0.648–0.790) and OI (AUC = 0.752. 95% CI = 0.684–0.819) significantly can predict mortality. On the other hand, a higher P/F ratio can predict survival (AUC = 0.734, 95% CI = 0.664–0.805). P/F ratio of 160 on day 1 can predict survival. Oxygen saturation index values above 10.4% and OI above 13.5% were the cutoff derived for day 1 values to predict mortality. Conclusion: Noninvasive OSI can be used to assess the severity of hypoxic respiratory failure in C-ARDS without arterial access in resource-limited settings. Oxygen saturation index can noninvasively provide prognostic information in invasively ventilated C-ARDS patients.