OBJECTIVE: To report a case of fatal liver failure possibly associated with concurrent use of bupropion and carbimazole. CASE SUMMARY: A 41-year-old Chinese man with a history of hyperthyroidism had been treated with carbimazole and propranolol for the past 5 years. He received a 10-day course of bupropion as an aid for smoking cessation 10 weeks prior to presentation. He developed acute liver failure with rapid deterioration of renal function. Liver biopsy showed evidence of nonspecific drug-induced acute liver injury. His condition was further complicated by sepsis and coagulopathy. Death resulted 19 days after the onset of symptoms. The likelihood that bupropion induced hepatotoxicity in our patient was possible, based on the Naranjo probability scale. DISCUSSION: Although there is increasing evidence of hepatotoxicity induced by bupropion, this is the first case of fatality that could have resulted from acute liver failure in a patient receiving bupropion while on concomitant treatment with carbimazole. CONCLUSIONS: Clinicians should be aware of the possibility of acute liver insult induced by bupropion given concurrently with other hepatotoxic drugs.