© 2013, Indian Society of Haematology & Transfusion Medicine. Objectives: To present a case of human monocytic ehrlichiosis (HME) that was complicated by macrophage activation syndrome (MAS), also known as secondary hemophagocytic lymphohistiocytosis (sHLH).Methods: Data was collected from patient’s electronic medical records at the University of Alabama at Birmingham. The patient is a part of a larger cohort of patients with all-cause MAS treated at our center.Case: A 63 year old renal transplant recipient male on maintenance immunosuppressive therapy presented with high grade fever, leukopenia, thrombocytopenia and elevated transaminases and initially met clinical criteria for severe sepsis. On further investigation, clinical and laboratory criteria for MAS were met. He was treated with a combination of doxycycline for HME and a novel combination of anakinra (interleukin-1 receptor antagonist), and high dose corticosteroids. The discussion focuses on clinical presentation, pathogenesis and treatment of MAS with an emphasis on MAS secondary to HME.Conclusion: Macrophage activation syndrome or sHLH is a dysfunctional, hyperactive and potentially fatal immune system response that results in multi-organ dysfunction. With increasing incidence of Ehrlichia chaffeensis as an emerging pathogen, clinicians should be aware of this fulminant and potentially fatal complication of HME.