The objective of the study was to report our institutional experience in the management of children and newborns with refractory septic shock who required venoarterial extracorporeal membrane oxygenation (VA ECMO) treatment, and to identify patient-and infection-related factors associated with mortality. This is a retrospective case series in an intensive care unit of a tertiary pediatric center. Inclusion criteria were patients ≤ 18 years old who underwent a VA ECMO due to a refractory septic shock due to circulatory collapse. Patient conditions and support immediately before ECMO, analytical and hemodynamic parameter evolution during ECMO, and post-canulation outcome data were collected. Twenty-one patients were included, 13 of them (65%) male. Nine were pediatric and 12 were newborns. Median septic shock duration prior to ECMO was 29.5 h (IQR, 20–46). Eleven patients (52.4%) suffered cardiac arrest (CA). Neonatal patients had worse Sepsis Organ Failure Assessment (SOFA) score, Oxygenation Index and PaO2/FiO2 ratio, blood gas analysis, lactate levels, and left ventricular ejection fraction compared to pediatric patients. Survival was 33.3% among pediatric patients (60% if we exclude pneumococcal cases) and 50% among newborns. Hours of sepsis evolution and mean airway pressure (MAP) prior to ECMO were significantly higher in the non-survivor group. CA was not a predictor of mortality. Streptococcus pneumoniae infection was a mortality risk factor. There was an improvement in survival during the second period, from 14.3 to 57.2%, related to shorter sepsis evolution before ECMO placement, better candidate selection, and greater ECMO support once the patient was placed. Conclusion: Patients with refractory septic shock should be transferred precociously to a referral ECMO center. However, therapy should be used with caution in patients with vasoplegic pattern shock or S. pneumoniae sepsis.What is Known:• Children with refractory septic shock have significant mortality rates, and although ECMO is recommended, overall survival is low.• There are no studies regarding characteristics of infections as predictors of pediatric survival in ECMO.What is New:• Septic children should be transferred precociously to referral ECMO centers during the first hours if patients do not respond to conventional therapy.• Treatment should be used with caution in patients with vasoplegic pattern shock or S. pneumoniae sepsis.