Necrotizing enterocolitis is the most common gastrointestinal emergency in neonates. The etiology is considered multifactorial. Risk factors include prematurity, enteral feeding, hypoxia, and bacterial colonization. The etiologic role of viruses is unclear. We present a case of necrotizing enterocolitis associated with cytomegalovirus and Proteobacteria in a 48-day-old, ex-premature infant and discuss the effects of potential viral-bacterial interactions on host susceptibility to this disease.