Background:The study tested the hypothesis that hyperoxemia and hypoxemia differentially alter cerebral blood flow velocity (CBFV) in a gestational age-dependent manner. Methods: Cases comprised 98 neonates with mild respiratory distress, receiving oxygen for >24 h in first 48 h of life. Ninety-eight age-and-weight-matched healthy neonates served as controls. Infants with perinatal asphyxia, shock, sepsis, malformations, acidosis/alkalosis, and hypo/hypercarbia were excluded. Resistance index (RI), pulsatility index (PI), peak systolic flow velocity (PSV), and vascular diameter were measured in internal carotid, vertebral, and middle cerebral arteries by transcranial doppler ultrasonography between 24 and 48 h of life with immediate postdoppler arterial blood gas analysis. For subgroup analysis, neonates were divided by gestational age and PaO 2 . results: An overall decrease in RI/PI and increase in PSV and vasodilation was observed in cases. Hyperoxemia (PaO 2 >90 mm Hg) was more common in premature neonates. Neonates <32 wk showed an increase in CBFV (decreased RI/PI and increased PSV/diameter) in association with hyperoxemia. An opposite response was observed in neonates ≥32 wk, where CBFV increased in response to hypoxemia (PaO 2 <50 mm Hg) and decreased in hyperoxemia. Increased CBFV showed high predictive accuracy for immediate mortality and intracranial hemorrhage. conclusion: Depending on gestational maturity, hyperoxemia or hypoxemia produce differential effects in CBFV.