Systemic Lupus erythematosus (SLE) is an autoimmune connective tissue disorder with multiple system involvements in which the cardiac system is commonly affected. Although pericarditis and pericardial effusion are prevalent cardiac manifestations in SLE but massive pericardial effusion as an initial presentation is unusual. We describe a 47-year-old woman presented to the hospital with headache, dry cough, shortness of breath and fatigue. According to the clinical, radiologic, echocardiography and laboratory rheumatologic tests findings SLE was proved and treatment with prednisolone, hydroxychloroquine and mycophenolate mofetil started. She improved clinically and follow up echocardiography showed reduction of the effusion volume in comparison to the previous ones within 6 months. In patients with cardiopulmonary symptoms specially when other organ involvements are seen, screening for autoimmune systemic diseases such as SLE should be considered. In order to achieve rapid recovery and preventing life-threating complications early diagnosis and treatment is essential.