Severe sepsis and septic shock are leading causes of morbidity and mortality in the pediatric population. Unlike what is suggested for the adult population, recombinant human activated protein C (rhAPC) is contraindicated in children. Long before rhAPC was considered for use in pediatric patients, case reports appeared on the safe administration of protein C zymogen. Therefore, we conducted a systemic review of currently available data on protein C zymogen (PC) use among children affected by severe sepsis or septic shock.A total number of 13 case series or case reports and a dose-finding study were found on the use of PC in the pediatric intensive care unit, reporting on 118 treated children, with an overall survival of 84%. There was no bleeding complication, the only reported complication being a single mild allergic reaction. These studies show that PC is safe, not associated with bleeding and possibly useful for improving coagulation abnormalities of sepsis.