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The ACCM/PALS guidelines address early correction of paediatric septic shock using conventional measures. In the evolution of these recommendations, indirect measures of the balance between systemic oxygen delivery and demands using central venous or superior vena cava oxygen saturation (ScvO2 ≥ 70%) in a goal-directed approach have been added. However, while these additional goal-directed endpoints are based on evidence-based adult studies, the extrapolation to the paediatric patient remains unvalidated.The purpose of this study was to compare treatment according to ACCM/PALS guidelines, performed with and without ScvO2 goal-directed therapy, on the morbidity and mortality rate of children with severe sepsis and septic shock.Children and adolescents with severe sepsis or fluid-refractory septic shock were randomly assigned to ACCM/PALS with or without ScvO2 goal-directed resuscitation.Twenty-eight-day mortality was the primary endpoint.Of the 102 enrolled patients, 51 received ACCM/PALS with ScvO2 goal-directed therapy and 51 received ACCM/PALS without ScvO2 goal-directed therapy. ScvO2 goal-directed therapy resulted in less mortality (28-day mortality 11.8% vs. 39.2%, p = 0.002), and fewer new organ dysfunctions (p = 0.03). ScvO2 goal-directed therapy resulted in more crystalloid (28 (20–40) vs. 5 (0–20) ml/kg, p < 0.0001), blood transfusion (45.1% vs. 15.7%, p = 0.002) and inotropic (29.4% vs. 7.8%, p = 0.01) support in the first 6 h.This study supports the current ACCM/PALS guidelines. Goal-directed therapy using the endpoint of a ScvO2 ≥ 70% has a significant and additive impact on the outcome of children and adolescents with septic shock.