A 57-year-old man with chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea (OSA) and no prior psychiatric history presented repeatedly over 6 months with mental and behavioural changes. Laboratory tests, chest X-ray and sleep study diagnosed an infective exacerbation of COPD, type II respiratory failure and OSA. Differential diagnoses included delirium, primary mania in bipolar affective disorder or organic pathology causing secondary mania. Oxygen, steroids, bronchodilators, antibiotics and non-invasive ventilation were administered to treat his infection and respiratory failure. However, blood gas analysis showed persistent hypoxia and hypercarbia, aggravating his ongoing mental state disturbance that required security supervision and sedation with antipsychotics and benzodiazepines. Sudden onset of classic manic symptoms and multiple presentations suggested secondary mania, driven by chronic hypoxia in end-stage COPD and OSA. The challenge was establishing a balance between mental state control and treatment of physical illness.