A 17-year-old girl presented with Neisseria meningitidis sepsis, with evidence of disseminated intravascular coagulation. Substitution therapy with both antithrombin and protein C concentrates was initiated, leading to clinical and biological improvement. Sequential dosages were performed for biological markers including thrombin-activatable fibrinolysis inhibitor (TAFI). Substitution therapy with both antithrombin and protein C concentrates led to a clinical and biological improvement. Biological markers showed a decrease in thrombin generation and in plasminogen activator inhibitor 1 (PAI-1) and a return of TAFI to a normal value. Discontinuation of substitutive treatment was marked by a clinical relapse at 24 h, with thrombin generation and increase in PAI-1, while TAFI remained unchanged. This report shows the evolution of hemostasis markers during septic shock and provides new data concerning the effects of a substitutive therapy.