Introduction: Decreased cerebral blood flow follows resuscitation from neonatal hypoxic/ischemic injury. We posit that reduced CBF is due to a change in NO and superoxide balance secondary to endothelial nitric oxide synthase (eNOS) uncoupling with vascular injury. Methods: Seven day old rats were subjected to cerebral hypoxia ischemia by unilateral carotid occlusion followed by hypoxia with hyperoxic or normoxic resuscitation. Expired CO₂was determined during resuscitation. Laser Doppler flowmetry was used to monitor cerebral blood flow, and cerebral perviascular NO and superoxide were determined using fluorescent dyes with fluorescence microscopy. The effect of tetrahydrobiopterin supplementation on each of these measurements and the effect of apocynin and L-NAME administration on NO and superoxide was determined. Results: CBF in ischemic cortex declined following onset of resuscitation with 100% O₂ but not room air. Expired CO₂ was decreased at the onset of resuscitation, but recovery was the same in normoxic and hyperoxic resuscitated groups. Peri-vascular NO induced fluorescence declined and superoxide induced fluorescence increased in the ischemic cortex up to 24 hours post-ischemia. L-NAME treatment reduced superoxide relative to non-ischemic cortex. Apocynin treatment increased NO and decreased superoxide. Tetrahydrobiopterin following the injury increased perivascular NO, reduced perivascular superoxide, and increased cerebral blood flow during hyperoxic resuscitation. Interpretation: Decreased CBF follows hyperoxic resuscitation but not normoxic resuscitation after neonatal hypoxic/ischemic injury accompanied by a reduction in perivascular production of NO and an increase in superoxide. Both NOS and NADPH-oxidase contribute to vascular free radical changes seen in cerebral hypoxic-ischemic injury.