The physiologic basis for relief from dyspnea after therapeutic thoracentesis remains poorly understood. Here, we describe the case of a 46-year-old man with large recurrent pleural effusion with absent perfusion to the affected lung who experienced dramatic dyspnea relief after large-volume thoracentesis. This patient's improvement in breathlessness cannot be attributed to improved gas exchange and suggests the primary physiologic basis for the relief in dyspnea is a change in respiratory system mechanics or work of breathing.