We report five cases of fatal bupropion overdose with post mortem bupropion concentrations ranging from 3.1 to >20 mg/L. Four patients had ingested a sustained-release formulation of bupropion and had evidence of pill “bodies” in their stomach with significantly elevated blood bupropion concentrations. The pills found in these patients may represent the residual matrix/shell with significant portions of the actual bupropion released and absorbed by the patients.