Spontaneous pneumothorax is a frequent situation in respiratory medicine, and its treatment is based on conservative treatment or pleural drainage. Reexpansion pulmonary edema (REPE) is often a mild complication following pneumothorax drainage. We report here a severe case of unilateral REPE following spontaneous pneumothorax drainage associated with major pulmonary plasmatic leakage. The clinical presentation was severe and sudden with respiratory and circulatory failures. Initial resuscitation was mostly based on prone and head-down positioning in association to fluid expansion and mechanical ventilation. On the basis of this clinical case report, we strongly suggest to think about severe pulmonary reexpansion edema when respiratory and hemodynamic failures occur few hours after pneumothorax-related efficient pleural tube drainage.