A 68-year-old man with no cardiovascular risk factors was admitted with a stroke because of multiple brain infarcts in different vascular territories. He required mechanical ventilation for hypoxia as a result of aspiration pneumonia. Subsequent recovery was hindered by episodic, unexplained hypoxia. Investigations excluded pulmonary embolism, pulmonary hypertension and severe lung diseases. Transthoracic echocardiography (TTE) with saline bubble contrast showed mild, delayed, right-to-left shunting, thought to represent an insignificant, intrapulmonary, non-cardiac shunt. Hypoxic episodes worsened, requiring admission from community rehabilitation hospital to our centre and another period of mechanical ventilation. Elevated alveolar-arterial gradients indicated a non-hypoventilatory cause. Repeat TTE bubble contrast study and transoesophageal echocardiography (TOE) demonstrated a patent foramen ovale (PFO) with large shunt potential, associated with an aneurysmal interatrial septum. This provided a unifying explanation for cryptogenic stroke and recurrent hypoxaemia. After percutaneous PFO closure hypoxic episodes ceased and he returned successfully to rehabilitation.