Background: Titration of inspired oxygen is a challenge in preterm infants with hypoxemic respiratory failure (HRF). Monitoring of brain oxygen by near infrared spectroscopy (NIRS) has been proven to minimize the burden of hyperoxia and hypoxemia, with better understanding of cerebral autoregulation (CAR). integrating NIRS and pulse oximetry (SpO2) for titrating inspired oxygen is a novel approach. Methods: We aimed to study the impact of integrated monitoring of oxygen saturation by SpO2 and cerebral regional tissue oxygen (crRTO) by NIRS during oxygen reduction test (ORT) on reducing oxygen requirement in preterm infants with HRF. The correlation between SpO2 with crRTO, and fractional oxygen extraction (FOE) was assessed, concordance levels (r>0.5) were determined during the assessment period, and was considered as a sign of impaired autoregulation. The primary outcome was the achievement of significantly lower FiO2 at 72 hours after start of the integrated monitoring. Results: Total of 38 preterm infants were included, 27 had normal cerebral autoregulation (CAR), (group 1) in whom SpO2 was poorly correlating with cerebral regional tissue oxygen (crRTO) with (r<0.5) and had significantly greater percentage of reduction below baseline in FiO2 (Mean:34%). Eleven infants had impaired CAR (group 2) with SpO2 significantly correlating with crRTO (r>0.5) and had a linear trend of FOE inverse to SpO2 and crRTO; this was considered as an arterial saturation dependent oxygen delivery (SadDO2). Conclusion: Integrated monitoring of preterm infants by SpO2 and crRTO was associated with easier weaning of oxygen with less burden of both hyperoxia and hypoxemia.