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How does a physician decide to use a recently FDA-approved life-saving device in a desperately ill child in which little prior clinical experience is available? This report presents a pediatric patient with neutropenic septic shock and multiorgan failure (MOF) with a 95% chance of death and the availability of a therapeutic device with a completely new approach to treat sepsis. This device, called the selective cytopheretic device (SCD), is a first-in-class autologous immune cell directed therapy. The SCD, when integrated into an extracorporeal blood circuit, has been shown to bind activated neutrophils and monocytes. With a simple pharmacologic maneuver within the device, the bound cells in real time are immunomodulated from a highly pro-inflammatory state to a less inflammatory phenotype. These transformed cells are then released back into the systemic circulation thereby tempering the systemic hyperinflammatory disorder. Since this cell directed therapy focuses on neutrophils, the processing of these cells in a neutropenic state may be a substantive risk resulting in further immunosuppression. On the other hand, the immunomodulation of the circulating neutrophils and monocytes, although sparse, may be beneficial to disrupt the dysregulated inflammatory state responsible for ongoing tissue damage and organ dysfunction. Prior clinical SCD trials excluded patients with neutropenia so that no prior clinical experience was available to make a difficult decision. This report presents the way the medical team approached these issues and made a therapeutic plan that resulted in a positive clinical outcome for the patient.