Neurological and neuroelectrophysio-biochemical profiles were evaluated in newborn lambs exposed to severe temporary asphyxia. Isoelectric EEG, marked disturbances of phosphorus magnetic resonance spectrum (31P-MRS), and significant brain intracellular acidosis (pHi) were noted during asphyxia. Following resuscitation, the presence of early postasphyxic blood-brain-barrier (BBB) opening was associated with a marked transient increase in intracranial pressure (ICP), a 50% neonatal mortality and a 67% incidence of severe asphyxic encephalopathy. In contrast, those lambs exposed to the same magnitude of asphyxia, but without early BBB opening experienced neither death nor severe neurological deficits. Further, these lambs showed a rapid progressive normalization of the 31P-MRS and pHi, despite, the lack of EEG recovery in the first hour following resuscitation. Thus, the present study depicts that the early postasphyxic BBB disruption following temporary neonatal asphyxia is associated with poor prognosis.