INTRODUCTION: Effects of breathing gas with elevated oxygen partial pressure (Po₂) and/or elevated inspired oxygen fraction (FIo₂) at sea level or higher is discussed. High FIo₂ is associated with absorption problems in the lungs, middle ear, and paranasal sinuses, particularly if FIo₂ > 80% and small airways, Eustachian tubes, or sinus passages are blocked. Absorption becomes faster as cabin altitude increases. Pulmonary oxygen toxicity and direct oxidative injuries, related to elevated Po₂, are improbable in flight; no pulmonary oxygen toxicity has been found when Po₂ < 55 kPa [418 Torr; 100% O₂ higher than 15,000 ft (4570 m)]. Symptoms with Po₂ of 75 kPa [520 Torr; 100% O₂ at 10,000 ft (3050 m)] were reported after 24 h and the earliest signs at Po₂ of 100 kPa (760 Torr, 100% O₂ at sea level) occurred after 6 h. However, treatment for decompression sickness entails a risk of pulmonary oxygen toxicity. Elevated Po₂ also constricts blood vessels, changes blood pressure control, and reduces the response to low blood sugar. With healthy lungs, gas transport and oxygen delivery are not improved by increasing Po₂. Near zero humidity of the breathing gas in which oxygen is delivered may predispose susceptible individuals to bronchoconstriction.Shykoff BE, Lee RL. Risks from breathing elevated oxygen. Aerosp Med Hum Perform. 2019; 90(12):1041-1049.