The brain is exceptionally reliant on a pervasive supply of oxygen, which is precisely matched to neural metabolic demand, via neurovascular coupling. Hypoxic exposure (high-altitude pursuits), challenges this coupled relationship. As oxygen saturations fall, global cerebral blood flow (CBF) increases to maintain cerebral oxygen delivery, mitigating any threat of decoupling between oxygen supply and demand. However, some brain regions, including the posterior cingulate cortex (PCC) have an unexpected decrease in CBF during acute hypoxia (1) suggesting a change in regional metabolism. Investigations of the cerebral metabolic rate of oxygen in hypoxia have shown a link to an increase in the concentration of the excitatory neurotransmitter glutamate (2) which has been related to changes in neural activity and the hemodynamic response (neurovascular coupling) (3,4). We hypothesised that if neurovascular coupling is unaffected by hypoxia, the regional reductions in CBF suggesting reduced regional neural activity, should be reflected via a decrease in glutamate levels. Understanding the effects of hypoxia on neurovascular coupling, and neurometabolism is important in understanding cognitive alterations that have been reported at altitude, and in pathologic conditions involving hypoxia. To test this, this study exposed 11 participants to a moderate hypoxic environment (Fraction of inspired oxygen [FIO2] = 0.12) for 3.5 hoursand a procedurally matched normoxia condition (FIO2=.209). After 2 hours resting in an environmental chamber, participants were placed into a 3 tesla MRI scanner whilst remaining in the hypoxic or normoxic condition. Whole brain resting state microvascular perfusion was quantified by Arterial Spin Labelling and the regional resting state neurochemical environment was measured by Magnetic Resonance Spectroscopy (MRS) within the PCC. Paired samples t-tests (cluster mass FWE correction at P<0.05) of the ASL data confirmed a reduction in perfusion during hypoxia compared to normoxia within the PCC and right posterior temporal cortex. In contrast MRS within the PCC revealed no significant change between normoxia and hypoxia in the excitatory neurotransmitter glutamate (p=0.9) or any other major metabolite including creatine (p=0.7) and n-acetyl aspartate (p=0.6). This supports our previous findings that indicate hypoxia induces a regional reduction in CBF within the PCC. Significantly, the PCC did not display a concomitant decrease in glutamate levels, or a change in other neurometabolites, that would infer a reduction in neural activity or metabolism. This challenges our present understanding of neurovascular coupling, whereby CBF is matched to demand, sustaining healthy neural functioning. Hypoxia appears to disrupt neurovascular coupling in a regionally specific manner, providing a mechanism to specific cognitive deficits experienced at altitude.