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Hemadsorption via the cytokine‐adsorber CytoSorb (CytoSorbents Europe, Berlin, Germany) has successfully been used as an adjunctive method in adults, mainly for the purpose of immunomodulation under acute inflammatory conditions such as sepsis and cardiac surgery. In recent years, there has been growing interest in its use in pediatric intensive care to improve outcomes in patients with multiple organ failure following an inflammatory illness. Literature on the application of CytoSorb in neonatal and pediatric patients is scarce, though the implication is that it could be an effective last‐resort treatment option in critically ill pediatric patients. Herein we present the clinical cases of two pediatric patients successfully treated with a combination of the CytoSorb hemadsorber, continuous renal replacement therapy, and extracorporeal membrane oxygenation due to multiple organ failure following different underlying medical conditions. Patient 1 was a 7‐month‐old male child with Down's syndrome admitted to the Pediatric Intensive Care Unit (PICU) after congenital heart surgery, who developed antimicrobial‐resistant septic shock and severe acute respiratory distress syndrome. Patient 2 was a 2‐year‐old male child admitted to the PICU with influenza A‐associated acute liver failure resulting in hyperammonemia, lactate acidosis, hemodynamic instability, and acute kidney failure. In both patients, hemadsorption with CytoSorb was initiated as an adjunctive rescue therapy to treat refractory multisystem organ failure. Improvement of laboratory and clinical parameters was observed within hours of treatment initiation. The application of the hemadsorber—developed for use in adults—proved simple and safe for use in both of our low‐weight pediatric patients. [ABSTRACT FROM AUTHOR]