Background: This study sought to evaluate the main causes of hospitalization of patients with systemic lupus erythematosus (SLE) in a tertiary health center in Saudi Arabia.Methods: A retrospective observational study was performed for all the SLE patients admitted to King Saud Medical City between 2016 and 2019. The primary reason for hospitalization was determined by the primary physician caring for the patient at the time of admission.Results: Of the 98 hospitalizations for SLE, 49% of patients were admitted from the emergency department (ED) and 51% from the rheumatology clinic. The most common reason for hospitalization was lupus flare (68.4%) followed by infection (20.4%). The lupus flare patients commonly presented with musculoskeletal (MSK) symptoms (34.6%), renal manifestations (25.5%), and skin rash (24.5%), whereas patients admitted with infection were commonly diagnosed with community-acquired pneumonia (12.2%). Other hospitalization causes were obstetric complications, adverse drug reactions, and thrombosis. Intensive care unit (ICU) admission was necessary for 7% of patients due to acute respiratory distress syndrome (ARDS) and pulmonary hemorrhage (28.6%) or other reasons (14.1%), such as pleural effusion, cardiac tamponade, and thrombotic thrombocytopenic purpura (TTP).Conclusions: The two most common reasons for SLE hospitalization were lupus flare and infection. Lupus flare was mainly due to MSK, renal, and dermatologic manifestations. The most common infection leading to hospitalization was community-acquired pneumonia, and ICU admission was mainly due to ARDS and pulmonary hemorrhage.