Refractory AIHA in pediatric patients is a challenging disease that forces us to weigh up the risks and benefits of heavy and prolonged immunosuppressive therapies that can reduce or even eradicate the hemolysis, despite the risk of infectious complications. For this reason, we feel that prolonged viral and fungal prophylaxis therapy should always be considered, during and after the immunosuppressive therapy. Furthermore, strict clinical monitoring should be carried out, even when no evident symptoms are present. In our patient, we did not administer any prophylaxis and clinical monitoring was probably delayed for too long after discharge. Resolution of the infectious complication was possible thanks to an advanced intensive care assistance, which consisted of ECMO and the management of its related complications.