We report a case of Guillain-Barré syndrome (GBS) accompanied by optic neuritis and a central white matter lesion subsequent to Epstein-Barr virus (EBV) infection. A 49-year-old man presented with visual disturbance and hemiparesis one week after developing cold-like symptoms. T2-and diffusion-weighted brain MRI showed a high-signal intensity lesion in the left internal capsule. The patient’s visual acuity improved during steroid pulse therapy, but his hemiparesis progressed to quadriparesis. Nerve conduction studies showed demyelination predominant in the distal nerve terminals, consistent with GBS. Serological testing suggested EBV reinfection. Our findings indicate that EBV-related central and peripheral demyelination can occur simultaneously and can be successfully treated with a combination of corticosteroids and immunoglobulin.