CD8+ encephalitis is a rare condition that can occur in patients with HIV. In Colombia, a case of this encephalitis was confirmed for the first time using flow cytometry of cerebrospinal fluid. The patient was a 50-year-old man with HIV and liver cirrhosis who discontinued antiretroviral therapy. Symptoms included disorientation, bradyphrenia, headache, problems with speech, memory, abstraction, ataxia, and chorea. Brain MRI showed bilateral asymmetric leukoencephalopathy, lumbar puncture revealed lymphocytic pleocytosis. Flow cytometry confirmed the diagnosis of CD8+ encephalitis when 42 cells (59.73% CD8+) were identified. The patient improved after treatment with corticosteroids. Diagnosis is usually confirmed by brain biopsy, but flow cytometry may be an alternative.