Hemophagocytic lymphohistiocytosis (HLH) is associated to high mortality and morbidity. A condition often underrecognized, HLH should be in the differential diagnosis of patients presenting with fever, cytopenia, hypertriglyceridemia and high ferritin levels (> 500 μg/L). Acquired or secondary HLH in adults is a heterogenous disease triggered by infectious, autoimmune, or neoplastic conditions. Infection associated HLH (IAHS) have been described in association to immunodeficiency and secondary to infections with endemic pathogens. Extensive investigation with microbiology, serology, urine antigens and biopsies of the bone marrow, lung or lymph nodes are often necessary. We present a series of three adult cases of HLH in patients admitted to the intensive care unit with a presumptive diagnosis of sepsis. Early recognition and treatment of this infection sometimes with concomitant administration of immunosuppressant therapy could impact the high mortality associated to this overlap syndrome.