Exogenous ketones are a supplemental form of ketone bodies that rapidly alter metabolism, providing extrahepatic tissues with an alternate fuel source, and can affect blood gases and pH balance. This thesis investigated whether consumption of exogenous ketone supplements (EKS) can be applied as a countermeasure to hypoxic exposure by mitigating the decline in oxygen saturation and cognitive performance as hypoxic exposure has shown to decrease both physical and cognitive performance. Study 1: Investigated the effects of various forms of EKS on metabolism, blood gases, respiration, heart rate variability, hemodynamics, and cognitive performance in healthy male and female populations at rest. Findings include rapid effects on metabolism, blood gases, pH, and no effect on cognitive performance. Study 2: Investigated the application of a ketone monoester (KME) as a potential countermeasure for oxygen saturation and cognitive declines during severe hypoxic exposure (6096 m, 9.7%O2 for 20 min) in healthy male participants at rest. Findings included enhanced resiliency to the declines in oxygen saturation and cognitive performance after KME ingestion. Study 3: A follow-up investigation to the prior study evaluated a lower dose of KME and a different domain of cognitive performance (vigilance/attention) during severe hypoxic exposure (6096 m, 9.7%O2 for 15 min) in healthy male participants at rest. Findings included enhanced resiliency to the declines in oxygen saturation and cognitive performance after KME ingestion. Study 4: Investigated the use of KME as a countermeasure to declines in oxygen saturation, cognitive performance, and effects of subjective exercise intensity during severe hypoxia at rest and during moderate intensity exercise in healthy males. Findings included enhanced resiliency to the decline in oxygen saturation, but no effect on cognitive performance after KME ingestion. Collectively, these investigations show promise for KME as a countermeasure for acute exposure to severe hypoxia both at rest and during exercise, with further work needed to establish optimal dosing and effectiveness in other populations and specific use cases.