Progressive multifocal leukoencephalopathy (PML) is a rare, serious, and usually fatal demyelinating disease that occurs predominantly in severely immunosuppressed patients. The disease is caused by the infection of oligodendrocytes with JC virus that is widely distributed as a latent infection in the general populations. PML has been described mainly in patients infected with the human immunodeficiency virus. However, other immune-suppressed patients including malignancies and organ transplants can be affected with JC virus infection. Recently it is suggested that rheumatologic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis, dermatomyositis, polymyositis, wegener`s granulomatosis be known to be at risk of developing PML. We report a case of PML in a patient with SLE.