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Introduction: Platypnea–orthodeoxia syndrome is a rare, posture-dependent dyspnea in which upright hypoxemia relieved when supine results from a right-to-left intracardiac shunt, most commonly a patent foramen ovale (PFO). Present in up to 25 % of adults, a PFO is typically silent, but age-related anatomical changes can permit systemic desaturation. Fewer than 150 cases are documented, so clinical recognition remains limited. Methods: Case report Results: A 69-year-old woman with arterial hypertension, asthma, heart failure, and hypothyroidism was admitted for progressive dyspnea that eventually occurred at rest. Examination revealed tachypnea, diminished breath sounds, and basal crackles; pulse oximetry showed oxygen saturation down to 70%. Arterial blood gas analysis confirmed severe hypoxemia (PaO2 52 mm Hg) without acid–base disturbance. A presumed severe asthma exacerbation was treated with bronchodilators, systemic corticosteroids, and high-flow nasal-cannula oxygen. Chest radiography demonstrated bilateral perihilar interstitial opacities without consolidation or air trapping. On transfer to the intensive care unit, persistent hypoxemia despite clinical improvement precluded weaning from oxygen therapy. Computed-tomographic pulmonary angiography excluded pulmonary embolism but revealed mild pulmonary fibrosis. Transthoracic echocardiography showed a mildly reduced LVEF of 43% with regional wall-motion abnormalities. Marked desaturation when upright that normalized supine and prone suggested platypnea–orthodeoxia. Transesophageal echocardiography confirmed a 7 mm PFO with a 13 mm tunnel and spontaneous microbubble passage without Valsalva, indicating a right-to-left shunt. Percutaneous closure of the PFO with an Amplatzer device normalized oxygen saturation. Conclusions: Platypnea–orthodeoxia syndrome arises from the coexistence of a patent foramen ovale and anatomic or functional factors that facilitate a right-to-left atrial shunt. Evidence indicates that increased venous return from the inferior vena cava and deformation of the inter-atrial septum can promote the abnormal passage of deoxygenated blood into the systemic circulation. Contrast echocardiography is the diagnostic modality of choice, and percutaneous PFO closure has been shown to relieve symptoms and restore normoxemia in most patients.