The authors observed the effect of drotrecogin alfa (activated) in a case of pediatric severe sepsis. A 4-month-old male infant with Serratia marcescens septic shock, multiple organ dysfunction syndrome (MODS), and consumptive coagulopathy was admitted. The safety and efficacy of drotrecogin alfa (activated) has not yet been established for patients younger than 18 years of age. This is the first published report of the use of drotrecogin alfa (activated) in an infant with severe sepsis. Within 6 hours of starting therapy, there was a significant improvement in hemodynamics, which was not maintained after the drotrecogin alfa (activated) infusion was temporarily discontinued. No significant bleeding complications occurred during the infusion. A brain MRI on day 22 after drotrecogin alfa (activated) infusion showed bilateral small occipital hemorrhages. Drotrecogin alfa (activated) in this infant was temporally related to significant improvement. It is unknown whether the MRI brain lesions are related to severe sepsis with disseminated intravascular coagulation or drotrecogin alfa (activated) infusion. The authors believe that drotrecogin alfa (activated) should be considered in select children with life-threatening severe sepsis.