Extracorporeal membrane oxygenation (ECMO) is widely used for cardiopulmonary support in neonates with cardiopulmonary failure secondary to overwhelming sepsis. The purpose of this study was to examine the effects of culture status on the eventual outcome of septic neonates requiring ECMO support. Data from the Extracorporeal Life Support Organization (ELSO) for the tears 1990 through 1992 inclusive were collected and analyzed for all neonates with a primary diagnosis of sepsis. Records were reviewed for gestational age, birth weight, culture status and isolated organism, last arterial blood gas before beginning ECMO, hemorrhagic complications during bypass, and overall survival. Gram-positive sepsis accounted for 85% of positive cultures. Group B streptococcus (GBS) and Escherichia coli were the most commonly isolated organisms (GBS: 95% of all gram-positive sepsis; E coli: 76% of all gram-negative sepsis) from culture-positive patients. Culture-negative patients were found to have a significantly lower mortality rate compared with culture positive patients (16.6% versus 26.9%, P < .001). The incidence of intracranial hemorrhage (ICH) was greater in culture-positive neonates when compared with culture negative (27.6% versus 20.1%, P < .05). There was no difference in the incidence of ICH or eventual outcome between gram-positive and gram-negative sepsis. The culture-positive, septic neonate who requires ECMO support appears to be at an increased risk for intracranial hemorrhage and death. Intracranial hemorrhage appears to be the primary factor affecting survival in these patients. The etiologic organism does not affect the incidence of ICH or outcome. Frequent head ultrasounds and strict control of coagulation parameters are recommended in this patient population.