Detection of cerebral hypoxia-ischemia (H-I) and prevention of brain injury remains problematic in critically ill neonates. Near-infrared spectroscopy (NIRS), a noninvasive bedside technology could fill this role, although NIRS cerebral O(2) saturation (Sc(O2)) viability-time thresholds for brain injury have not been determined. We investigated the relationship between H-I duration at Sc(O2) 35%, a viability threshold which causes neurophysiological impairment, to neurological outcome. Forty-six fentanyl-midazolam anesthetized piglets were equipped with NIRS and cerebral function monitor (CFM) to record Sc(O2) and electrocortical activity (ECA). After carotid occlusion, inspired O(2) was adjusted to produce H-I (Sc(O2) 35% with decreased ECA) for 1, 2, 3, 4, 6 or 8 h in different groups, followed by survival to assess neurological outcome by behavioral and histological examination. For H-I lasting 1 or 2 h, ECA and Sc(O2) during reperfusion rapidly returned to normal and neurological outcomes were normal. For H-I more than 2-3 h, ECA was significantly decreased and Sc(O2) was significantly increased during reperfusion, suggesting continued depression of tissue O(2) metabolism. As H-I increased beyond 2 h, the incidence of neurological injury increased linearly, approximately 15% per h. A viability-time threshold for H-I injury is Sc(O2) of 35% for 2-3 h, heralded by abnormalities in NIRS and CFM during reperfusion. These findings suggest that NIRS and CFM might be used together to predict neurological outcome, and illustrate that there is a several hour window of opportunity during H-I to prevent neurological injury.