INTRODUCTION: A recent U-2 fatigue study, in which 10 subjects completed 2 simulated long-duration missions breathing either 100% oxygen or air in a hypobaric chamber, offered an opportunity to compare subjects’ pulmonary function before and after remaining seated in a confined cockpit for 12 h.METHODS: In one U-2 mission configuration, the subject wore a full pressure suit and breathed aviator’s breathing oxygen while chamber pressure was maintained at 4572 m (15,000 ft) above mean sea level. In the second mission configuration, subjects wore standard aircrew flight equipment and breathed air while chamber pressure was maintained at 2438 m (8000 ft) above mean sea level. Subjects’ pulmonary function was assessed before and after the mission using four metrics: forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, and forced expiratory volume in 1 s/forced vital capacity ratio.RESULTS: Subjects showed significant declines for all four pulmonary metrics (2.7%, 6.4%, 13.9%, and 3.5%, respectively) after 12 h seated in the cockpit in both full pressure suit and aircrew flight equipment conditions.DISCUSSION: While the declines at both altitudes amounted to modest percentages of subjects’ total pulmonary capacities, they emerged after a single, acute sedentary exposure and appear to be unrelated to the percentage of oxygen in the breathing gas. This might have operational implications in confined mission environments where physiological demands are interspersed with long periods of inactivity.Beer J, Dart TS, Fischer J, Kisner J. Pulmonary effects from a simulated long-duration mission in a confined cockpit. Aerosp Med Hum Perform. 2017; 88(10):952–957.