The pathogenesis of necrotizing enterocolitis (NEC) remains poorly understood. We aimed to assess the extent of bacterial infection in the pathogenesis of NEC using serial procalcitonin measurements. Blood samples were drawn during the first 4 days following every clinical event requiring a workup for presumed NEC. Eight episodes were confirmed as NEC, 7 of which showed procalcitonin levels <1 ng/ml at presentation and <1.3 ng/ml thereafter, comparable to 24 healthy controls. The one infant with elevated procalcitonin had bacteremia in addition to NEC. Procalcitonin levels of 24 matched septic infants were higher than those of NEC infants, peaking at 4.1 ng/ml. We conclude that low procalcitonin values are the rule during episodes of NEC and provide further evidence that overactive local immune response, and not active infection, is primarily responsible for the mucosal damage in NEC.