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The Seraph-100™ is a purification filter that blunts cytokine storm, providing a more favorable environment to establish immune homeostasis. We present a novel case of compassionate use of Seraph filter in a young, healthy active duty service member with heat injury-induced massive inflammatory response. The patient is a previously healthy 26-year-old male with altered mental status, tachycardia, fever to 40.3 °C, and hypotension after losing consciousness during a 4-mile run. He had a history of one heat injury in college and took no medications or supplements. Initial workup demonstrated hemoconcentration, leukocytosis, and hyperkalemia. He was intubated, received isotonic crystalloid fluid, and was admitted to the intensive care unit. The patient developed vasopressor-resistant shock and multiorgan failure with rhabdomyolysis requiring continuous renal replacement therapy. The addition of the Seraph resulted in improved hemodynamic stability, decreased inflammatory markers, and improved organ function. Approximately 1 week after the final Seraph treatment, the patient had an abrupt massive lower gastrointestinal bleed and was transitioned to comfort care by family. We present the novel use of Seraph in the setting of multiorgan failure and hyperinflammatory state due to heat injury. The patient's vasopressor refractory distributive shock was believed to be secondary to heat stroke-induced massive inflammatory response, leading to a trial of Seraph therapy. This case demonstrates that the Seraph filter has the potential to improve hemodynamic instability and reduce cytokine storm in nonsepsis patients. [ABSTRACT FROM AUTHOR]