The administration of drotrecogin alfa (activated) improves outcome in adult patients with severe sepsis. Since the published pediatric experience with this drug is limited, the role of drotrecogin alfa (activated) in children, and especially in newborns is not well established. We describe a 3-day-old neonate with septic shock and multiorgan system failure, including circulatory, respiratory, renal failure, and disseminated intravascular coagulation, refractory to intensive fluid resuscitation and inotrope support. Within hours of drotrecogin alfa (activated) administration, the neonate experienced dramatic improvement in hemodynamic parameters. The infusion was discontinued after 48 hours, without clinical deterioration. Aside from transient thrombocytopenia, no significant side effects were observed. A brain MRI performed on day 18 after discontinuation of treatment was normal. The positive hemodynamic effect and outcome of treatment in this patient, indicates that drotrecogin alfa (activated) may play a similar role in the treatment of sepsis in neonates as already established in adults.