The macrophage activation syndrome (MAS) is a rare but potentially fatal disease. We report two cases of Crohn´s disease, one under 5-aminosalicylic acid and the other under corticosteroid, having developed MAS. The first was a male patient hospitalized for high fever, clinical examination found fever and left inguinal lymph node. The second case was a female patient hospitalized for asthenia, clinical examination found fever and oral mycosis. The biology tests revealed bi/pancytopenia, hyperferritinemia, hypofibrinogenemia. The myelogram showed hemophagocytosis. The identified infectious cause was Klebsiella pneumoniae in the urinary tract in one patient and oral Candida albicans in the other one. Thoraco-abdomino-pelvic computed tomography (CT) scan showed a thickening of the bladder in the male patient, and eliminated a deep infection and tumour cause in the female patient. The diagnosis of MAS was made, and both patients were placed on broad-spectrum antibiotic, in addition to local antifungal treatment and corticosteroid for the female patient, but the evolution was fatal for both. In conclusion, the management of MAS should be fast and multidisciplinary, based on treatment of the causal infectious agent, immunomodulatory treatment of haemophagocytosis, symptomatic treatment and replacement of organ failure.