Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder involving multiple organ systems and can often present in the emergency department (ED). Fever, joint involvement, and skin rash are the classical features, and the disease can affect multiple organ systems. Malar rash, bullous eruptions resembling toxic epidermal necrolysis, urticaria, angioedema, and vasculitic involvement are the cutaneous manifestations presenting in the ED. Emergencies can occur due to various organ involvement (hematologic, renal, gastrointestinal, cardiovascular, pulmonary, neuropsychiatric, and rheumatologic). Invasive infections can occur due to adverse effects of various medications used in SLE (prolonged or high-dose corticosteroids, immunosuppressives). Causes of mortality in LE emergencies are commonly related to infections and antiphospholipid syndrome (APS). APS manifests with clinical features of thrombosis (venous, arterial, and microvascular) and pregnancy-related complications. In pregnancy, there may be flares of lupus, active lupus nephritis, APS-related complications, and bad obstetric outcome. Neonatal lupus may present as heart block with or without cardiomyopathy. Various serological tests, imaging studies, and tissue biopsies are done based on the relevance of the clinical manifestations. The extent of organ damage rather than the disease activity determines the mortality, and a multidisciplinary approach should be adopted for effective management in SLE emergencies.