Background: Hemophagocytic lymphohistiocytosis (HLH) has been reported to complicate fulminant tropical infections but data on severe HLH with multi-organ dysfunction (MODS) are scant. Materials and Methods: Retrospective review of medical electronic records of our intensive care unit (ICU) over a 2-year period. Results: We describe 10 adult patients with HLH and MODS. Patients had short symptom duration prior to presentation and had rapid deterioration during their hospitalization course. Fever, organomegaly, neurologic abnormalities, hepatic abnormalities, and cutaneous signs were very common. No patient had diagnosed HLH at ICU admission (median 4 criteria [Inter Quartile Range 2-4.25]). All patients required mechanical ventilation and 80% required vasopressors. Infection-associated HLH (IAHS) was the most common etiology (80%). Seventy percent (7/10) of patients were treated with steroids and 20% received intravenous immunoglobulin. Etoposide and/or cyclosporine were administered in 20% (2/10). Nosocomial infections occurred in 40% and the ICU mortality was 70%. Conclusions: Severe HLH with MODS has a very high mortality. Data on adult cohorts with IAHS in the tropics with defined treatment protocols are urgently needed.