A 13-year-old boy with a background of Prader-Willi syndrome (PWS) was admitted to the regional paediatric intensive care unit, with community-acquired pneumonia. Despite a week of intravenous antibiotics, resolution of inflammatory markers and resolving consolidation on radiograph, he remained feverish. Fever of unknown origin investigations were negative and he was diagnosed with central thermal dysregulation secondary to hypothalamic dysfunction in PWS. Following a hyperpyrexia period, secondary rhabdomyolysis and renal failure developed. This was successfully managed with active cooling, ventilation and haemofiltration. After weaning from haemofiltration, the patient was successfully extubated to non-invasive respiratory support.