Human herpesvirus-6 (HHV-6) is a common virus that can cause nearly universal infection in infancy and early childhood. It typically manifests as an acute febrile illness. We describe a case of a premature infant with congenital hydrocephalus secondary to aqueductal stenosis with a ventriculoperitoneal shunt in place who developed intermittent fevers while she was admitted to the neonatal intensive care unit. She was ultimately diagnosed with acute HHV-6 meningitis. In addition to this report, we present a literature review regarding this virus’s potential modes of transmission and forms of clinical presentation in the neonatal period.