A 30-year-old Honduran male with recently diagnosed AIDS presented with a 1-month history of worsening abdominal pain, diarrhea, and fever. Initial investigations were notable for Cytomegalovirus viremia and diffuse lymphadenopathy. Axillary lymph node biopsy demonstrated necrotizing lymphadenitis with disseminated histoplasmosis. Despite aggressive antimicrobial therapy he continued to clinically deteriorate raising suspicion for hemophagocytic lymphohistiocytosis. The patient met 5 of 8 HLH-2004 diagnostic criteria and was successfully treated with dexamethasone and etoposide per the HLH-94 protocol. Despite the high mortality rates and poor clinical outcomes of hemophagocytic lymphohistiocytosis in patients living with HIV/AIDS, this case demonstrates that this high-risk patient population can be successfully treated and survive acquired hemophagocytic lymphohistiocytosis. Furthermore, our case stresses the importance of maintaining a broad differential diagnosis in patients living with HIV/AIDS who present with sepsis.