AbstractGiven the widespread availability of pulse oximetry and its potential to replace partial pressure of arterial oxygen (PaO2)-based indices of oxygenation, we aimed to study the correlation between pulse oximetry-based oxygen saturation (SpO2)- and PaO2-based indices of oxygenation namely, SpO2/FiO2 (SF) ratio with PaO2/FiO2 (PF) ratio and oxygen saturation index (OSI) with oxygenation index (OI) under varying physiological conditions, along with accuracy measures for SpO2-based indices. Inclusion criteria included children (1 month to 18 years) admitted to pediatric intensive care unit needing invasive ventilation for hypoxemic respiratory failure with SpO2 ≥ 80% and having an indwelling arterial catheter. A total of 1,237 sets of simultaneous PaO2, SpO2 readings, and ventilator parameters were recorded. There was a moderate correlation between SF and PF ratios (r s = 0.68, p < 0.001) and strong correlation between OSI and OI (r s = 0.89, p < 0.001). We obtained SF ratios of 271, 235, and 200 corresponding to PF ratios of 300, 200, and 100, respectively. SF ratio showed a good discrimination ability to identify moderate (area under the receiver operating characteristic curve [AUROC] = 0.901) and severe acute respiratory distress syndrome (ARDS; AUROC = 0.889) and fair discrimination ability for mild ARDS (AUROC = 0.770). OSI of 4.1, 6.4, and 11.1 corresponded to OI of 4, 8, and 16, respectively. OSI demonstrated an excellent discrimination ability for diagnosing mild (AUROC = 0.928), moderate (AUROC = 0.961), and severe ARDS (AUROC = 0.965). The correlation between SF/PF ratio and OSI/OI was the strongest in the lowest SpO2 range studied. SpO2-based indices of oxygenation could replace PaO2-based indices with reasonable accuracy for patients with SpO2 values ≥ 80%.