In this study, a new hybrid PET/MRI method for quantitative regional cerebral blood flow (rCBF) measurements in healthy newborn infants was assessed and the low values of rCBF in white matter previously obtained by arterial spin labeling (ASL) were tested. Four healthy full-term newborn subjects were scanned in a PET/MRI scanner during natural sleep after median intravenous injection of 14 MBq 15O-water. Regional CBF was quantified using a one-tissue-compartment model employing an image-derived input function (IDIF) from the left ventricle. PET rCBF showed the highest values in the thalami, mesencephalon and brain stem and the lowest in cortex and unmyelinated white matter. The average global CBF was 17.8 ml/100 g/min. The average frontal and occipital unmyelinated white matter CBF was 10.3 ml/100 g/min and average thalamic CBF 31.3 ml/100 g/min. The average white matter/thalamic ratio CBF was 0.36, significantly higher than previous ASL data. The rCBF ASL measurements were all unsuccessful primarily owing to subject movement. In this study, we demonstrated for the first time, a minimally invasive PET/MRI method using low activity 15O-water PET for quantitative rCBF assessment in unsedated healthy newborn infants and found a white/grey matter CBF ratio similar to that of the adult human brain.