Although acute HIV-induced HLH is rare in literature, HIV is an important differential diagnosis in patients with HLH. In our study, a 33-year-old previously healthy male patient was admitted with fever of unknown origin, lymphadenopathy, generalized edema, transaminitis, acute renal failure, oliguria, myalgias, night sweats, unintentional weight loss, and leukopenia. Disease course was indicative of a viral-like prodrome of roughly 2-month duration. At an outside hospital, full viral work-up (including EBV, CMV, HIV antibodies, hepatitis panel) was negative. HIV p24 antigen assay was not available at the outside facility. Outside liver chemistry and lymph node biopsy were suggestive of HLH. HLH was confirmed via serum ferritin, white cell receptor, and cytokine studies. Repeat viral and rheumatologic studies revealed a positive p24 antigen with indeterminant HIV antibody. We demonstrate efficacy of a specific treatment plan as well as importance of p24 antigen studies in patients with HLH and/or the HIV window-period, adding to available literature/documentation of a rare disease process.