We reported a patient with neonatal herpes simplex encephalitis in whom diffusion-weighted imaging was performed repeatedly. Diffusion-weighted imaging at 20h after the onset of seizures revealed scattered small spotty high intensity lesions in both hemispheres and a high intensity area in the left fronto-temporal lobe. There was no abnormal finding on conventional magnetic resonance imaging. Second diffusion-weighted imaging 72h after the onset revealed expanded scattered high intensity lesions in the bilateral hemisphere, a high intensity area in the left fronto-temporal lobe, and a new high intensity area in the right temporal lobe. There was no report on neonatal herpes simplex encephalitis that showed scattered high intensities in diffusion-weighted imaging. Scattered small high intensities on diffusion-weighted imaging may suggest endothelial cell infection with swelling and small vessel necrosis. Early diffusion-weighted imaging will be valuable for early detection and diagnosis of neonatal herpes simplex encephalitis.