The prevalence of drug-associated toxic encephalopathy is unknown, but it is an uncommon condition. Toxic leukoencephalopathy was described associated with heroin consumption, it has been less commonly described with the use of cocaine and there are no reports of its association with consumption pasta base of cocaine (PBC). We report two females aged 31 years and a male aged 19 years, consumers of PBC who developed a fatal toxic leukoencephalopathy. They initiated their disease with severe and persistent headache, sequential focal neurologic deficits and a progressive impairment of consciousness that culminated with their death. Laboratory parameters such as blood count, cerebrospinal fluid analyses or infectious biological indices were normal. MRI showed multifocal lesions in brain white matter of both hemispheres confirming the leukoencephalopathy. There was no response to the use of methylprednisolone.