A 42-year-old pediatric intensive care unit physician traveled to Nepal and took a helicopter trip to Everest Base Camp. The helicopter reached an altitude of 5500 m during flight and descended at different destinations with varying altitudes. At Hotel Everest View at 3820 m, his oxygen saturation was 79%. He had mild tachypnea and deep breathing but was able to walk around, jump, and take photographs. He returned to Kathmandu (altitude, 1324 m) without using any supplemental oxygen during the entire trip. Based on calculations with the alveolar gas equation, he observed that he and his fellow passengers probably had hypoxemia during the trip. In summary, temporary hypoxemia associated with high altitude in healthy individuals without cardiorespiratory compromise may not require oxygen therapy. In contrast, intensive care unit patients who have respiratory failure may have similar oxygen saturation levels but may require oxygen therapy and mechanical ventilation. The oxygen saturation level must be interpreted in consideration of the clinical scenario before deciding about the need for oxygen therapy.