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Two cases of severe unexplained fatigue with mid-facial pain and rhinitis are presented. Sinus computerized tomography (CT) findings were minor, but both responded to functional endoscopic nasal surgery with resolution (Case 1) or near resolution (Case 2) of chronic fatigue. Possible mechanisms linking nasal disease and chronic fatigue include reflex etiology and sleep disturbance associated with abnormal nasal airflow. Often not considered by the primary care physician in differential diagnosis of fatigue, chronic sinusitis should be explored as a cause in unexplained cases.