Platypnea-orthodeoxia syndrome is a rare condition characterized by positional dyspnea and hypoxemia, with symptoms presenting in the upright position and improving when recumbent. Hypoxemia in platypnea-orthodeoxia syndrome is defined as a drop in Pao2 of more than 4 mm Hg or oxygen saturation greater than 5% when moving from a supine to an upright position. Etiologic mechanisms include intracardiac or pulmonary shunts and ventilation perfusion ratio mismatch. Platypnea-orthodeoxia syndrome has been described as part of COVID-19 pneumonia sequelae, with differing physiologic mechanisms from cardiac pathologies. This report presents the case of a patient with platypnea-orthodeoxia syndrome of multifactorial etiology: intracardiac shunting secondary to a patent foramen ovale and ventilation perfusion ratio mismatch as a sequela of COVID-19 pneumonia.