Introduction: Macrophage activation syndrome (MAS) is a rare but aggressive life-threatening auto-immune disease. It is characterized by fever, rash, splenomegaly, blood cytopenia, hypertriglyceridemia, high ferritin levels, liver insufficiency, coagulopathy and neurologic involvement. Persistent acti- vation of inflammatory cells like macrophages, natural killer cells and cyto- toxic lymphocytes can lead to a cytokine storm and multi organ damage. MAS is usually triggered by rheumatologic diseases and rarely in the presentation of a new connective disease like systemic lupus erythematosus (SLE). In addition to MAS, the auto-immune conditions of SLE can be associated with different overlapping syndromes notably dermatomyositis. Case description: We present a 31-year-old male from a Latin- American background without pre-existent conditions who presented complains of sore throat, joint pain, fever and fatigue. He quickly devel- oped a pancytopenia with increased liver and pancreatic enzymes. In the process of the investigation, he was treated with antibiotics and admitted intubated to the intensive care unit for a severe pneumonia. Result and conclusion: We proceeded with a bone marrow biopsy which detected an active MAS. Regarding his muscle weakness, we also revealed an inflammatory myositis on a quadricep muscle biopsy. Further discovery of positive auto-antibodies (ANA and anti-DNA) showed the presence of a LED. We successfully treated his different auto-immune complications with high doses of prednisone, and intravenously immunoglobulins. After 2 months of his admission and 12 days passed in the intensive care unit, the patient returned home with minimal sequelae with a long term immunosuppressive treatment of prednisone, mycophenolate mofetil and hydroxychloroquine. Take-home message: The early identification of the cause of MAS is crucial for the accurate management of this disease and preventing further multi organ complications. SLE has remains a complex condition that can present its first manifestations in a broad spectrum of auto-immune diseases.