Repetitive collapse of the upper airway during obstructive sleep apnea/hypopnea (OSA) exposes the brain of sufferers to frequent, transient, hypoxic episodes. The loss of cerebrovascular reactivity in sleep, and particularly in OSA, means that physiologic compensatory mechanisms may not ensure adequate brain oxygen levels. This (31)P magnetic resonance spectroscopy study, of 13 males with severe, untreated OSA undertaken after overnight sleep deprivation, represents the first, seconds time-scale analysis of human brain bioenergetics during transient hypoxia and demonstrates that a moderate degree of oxygen desaturation during sleep has significant effects on brain bioenergetic status. Oxygen desaturation >10% of sleeping baseline resulted in decreases in brain adenosine triphosphate levels (P<0.01), and increases in inorganic phosphate (P<0.0001) with no concomitant changes in phosphocreatine or brain pH. This indicates that the mechanism of adenosine triphosphate depletion in these patients is different to that observed in normoxic, awake working brain. These data show that the buffering capacity of phosphocreatine and the creatine kinase system is not active in mild transient hypoxia and that cerebrovascular compensatory mechanisms are not adequate to prevent decrements in brain high-energy phosphates in OSA. Transient hypoxia experienced during sleep may impair brain function more than previously thought.