To assess cerebral oxygenation in premature infants who are transitioning from nasal continuous positive airway pressure (nCPAP) to heated humidified high-flow nasal cannula therapy (HFNC). A prospective observational study done in a single-centre neonatal intensive care unit (NICU). Regional cerebral oxygen saturations (RcSO2 ) were measured using frequency-domain near-infrared spectroscopy (FD-NIRS) in very low birthweight (VLBW) premature infants born at <32weeks transitioning from nCPAP to HFNC. Median gestational age was 27weeks and median birthweight was 924g. Recordings were performed at a median gestational age of 30weeks and a median postnatal age of 10days. Median weight at study entry was 1111g. Cerebral oxygenation was not significantly different in infants transitioning from nCPAP to HFNC (66% vs 66%). No difference in cerebral oxygenation in premature infants transitioning from nCPAP to HFNC was observed. This finding is reassuring and further supports the use of HFNC in preterm infants.