A human immunodeficiency virus (HIV) type 2 (HIV-2)-infected African patient developed inflammatory demyelinating lesions of the optic nerves, spinal cord, and brain, which coincided with a decreasing CD4 cell count and with active HIV-2 replication. This case provides evidence that HIV-2 is neurotropic, extends the range of known HIV-2-associated neurological complications, and confirms the overlap between the neurological complications of HIV type 1 and HIV-2 infection.