Background: COVID-19 infection caused by the SARS-Cov-2 virus may result in severe acute respiratory failure and require respiratory support in the ICU.Objective: The present study was designed to evaluate the role of the respiratory rate oxygenation (ROX) index in the assessment of the adequacy of non-invasive respiratory support the COVID-19 patients with acute respiratory failure and observe its outcome.Materials and methods: This cross-sectional, observational study was conducted between October 2020 and September 2021 in the Department of Anaesthesia, Analgesia, and Intensive Care Medicine of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. A total of 44 patients with a confirmed diagnosis of COVID-19 with acute respiratory failure were enrolled in this study based on inclusion and exclusion criteria. Informed written consent was taken from the patient/patient’s guardian. Each patient underwent detailed history taking through physical examination and relevant investigations. All necessary information were recorded in a separate case record form. All the patients receiving high-flow nasal cannula (HFNC) were assessed at two hours, six hours, and 12 hours for variables of the ROX Index. The team of respective physicians was applied responsibly for determining HFNC failure to discontinue or deescalate respiratory support as a part of continuous positive airway pressure (CPAP) ventilation success. Each selected patient was observed for the duration of different types of respiratory support. CPAP failure or success, progression to mechanical ventilation, and data were collected from individual medical records. The patients who were successfully weaned from CPAP were recorded. The diagnostic accuracy of the ROX index was determined.Results: The mean age of the patients was 65±8.80 years with a majority in the age group 61-70 years (36.4%). A male predominance was observed with 79.5% male and 20.5% female. Of all, HFNC failure was observed in 29.5% of patients. Oxygen saturation (SpO2), respiratory rate (RR), and ROX index were statistically worse at the sixth and 12th hour of initiation of HFNC (P<0.05). At a cut-off value of 3.90, the ROC curve showed 90.3% sensitivity and 76.9% specificity in predicting HFNC success (the area under the curve (AUC) was 0.909). Similarly, 46.2% of patients had CPAP failure. SpO2, RR, and ROX index were found statistically worse among those patients at the sixth and 12th hour of CPAP therapy (P<0.05). The ROC curve showed 85.7% sensitivity and 83.3% specificity at a cut-off value of 2.64 in predicting CPAP success (the AUC was 0.881).Conclusion: The ROX index's clinical score form, which does not require lab findings or sophisticated computation techniques, is its key benefit. The study findings recommend the use of the ROX index to predict the outcome of respiratory support in acute respiratory failure in COVID-19 patients.