We used a high-flow nasal cannula with a patient who required a high fraction of inspired oxygen but could not tolerate a nasal or facial mask. We saw a 92-year-old woman with delirium and dementia in the intensive care unit for multi-lobar pneumonia with severe hypoxemia. Attempts to oxygenate the patient failed because she was unable to tolerate various facial and nasal masks. We then tried a high-flow nasal cannula (Vapotherm 2000i), which she tolerated well, and she had marked improvement in gas exchange and quality of life. The patient had severe health-care-associated pneumonia, accompanied by delirium and hypoxemia. It became apparent that the patient's death was imminent, and the goal of therapy was palliative. She had previously clearly expressed a desire not to undergo intubation and mechanical ventilation. In a situation where the patient was agitated and unable to tolerate a mask, the high-flow cannula reduced her agitation and improved her dyspnea, oxygenation, tolerance of oxygen therapy, and comfort at the end of life. Oxygen via high-flow cannula may enhance quality of life by reducing hypoxemia in patients who are unable to tolerate a mask but need a high oxygen concentration.