In this article, we present the case of a previously well 31-year-old man who sustained a mild closed-head injury following a motor vehicle incident and was admitted to the intensive care unit of a major teaching hospital. The man was sedated using propofol combined with midazolam and morphine as the main sedating agent. The propofol was started and continued at high dose for 8 days, over which time the patient deteriorated with metabolic acidosis, rhabdomyolysis, renal impairment, and cardiovascular collapse and then died. A forensic autopsy was performed. The only positive autopsy finding was a cardiac perivascular and interstitial infiltrate of mononuclear cells. The clinical and pathological features in the case presented were consistent with propofol infusion syndrome. No other cause for the above features was found and the cause of death was given as death related to propofol infusion syndrome.Propofol infusion syndrome is characterized by metabolic acidosis, rhadbomyolysis, and myocardial failure, sometimes with renal failure and hyperkalemia occurring in the setting of high-dose propofol treatment. The syndrome has become increasingly recognized in recent years. The syndrome is of importance to forensic pathologists who may see cases referred to their practice because of the unexplained deterioration of a patient in the intensive care unit and the association with head-injured patients and the pediatric population. Death associated with propofol infusion has not been described in the forensic literature.