Macrophage activation syndrome (MAS) is a rare manifestation of systemic lupus erythematosus (SLE) with potentially life-threatening consequences. To the best of our knowledge, this is the first case reported in literature for a constellation of MAS, glomerulonephritis, pericarditis, and retinal vasculitis as initial presentation of SLE. Despite extensive multisystem involvement of his disease, the patient responded well to initial steroid treatment, with mycophenolate mofetil successfully added as a steroid-sparing agent. Our case highlights the importance of multispecialty collaboration in the diagnosis and management of SLE with multisystem involvement.