BackgroundSystemic lupus erythematosus is a debilitating autoimmune disease with major contribution to the worldwide morbidity and mortality. This study aimed to investigate the causes of mortality in systemic lupus erythematosus (SLE) patients and the relation between clinical activity, disease-associated end-organ damage, laboratory markers and mortality.ResultsAmong the 771 patients who were successfully followed up, 34 patients (4.4%) died. The leading causes of death were infectious causes (35.29%), cardiopulmonary causes (26.48%), renal causes (14.7%), unknown causes (14.7%), neuropsychiatric causes (5.88%), and lastly gastrointestinal causes (2.94%). Subjects who died had lower complement 3 level, more anemia, lymphopenia, neutropenia, leukocytosis, thrombocytopenia, decreased glomerular filtration rate, higher incidence of infection, end-stage renal disease, and cardiopulmonary complications. Higher glucocorticoid dosage with more immunosuppressant (mofetil and cyclophosphamide) treatment was observed in patients who died. SLE disease Activity Index and Systemic Lupus International Collaborating Clinics damage index were both significantly higher in deceased persons. Multivariable hazards regression analysis revealed that lymphopenia (p = 0.017), decreased glomerular filtration rate < 50% (p = 0.002) with end-stage renal disease (p = 0.001), and high steroid daily use of > 40 mg (p = 0.016) were independent risk factors for the mortality of SLE patients.ConclusionInfections and cardiopulmonary complications are the leading causes of death in two centers caring for Egyptian SLE patients. Lymphopenia, end-stage renal failure, and high steroid daily use were associated with poor outcomes.