Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by malar rash, oral ulcers, arthralgia, photosensitivity and nephritis. Herein, we report a rare comorbidity, multiple avascular necrosis (AVN), in an adolescent SLE patient and also highlight the importance of risk factors for this comorbidity with a brief literature review. A 13-year-old female patient was admitted with severe headache, visual plus auditory hallucinations, polyarthritis and a history of recurrent oral ulcers. Acneiform malar rash, arthritis, cytopenia, low complement levels and autoantibody positivity yielded SLE diagnosis. We diagnosed her as having multifocal AVN after the 4th dose of cyclophosphamide, with bilateral knee pain and swelling and typical geographical lesions on magnetic resonance imaging. Avascular necrosis is a rare comorbidity of SLE and neuropsychiatric involvement, cyclophosphamide administration and severe disease may be the possible risk factors in addition to corticosteroid use. Further multicenter studies investigating the possible risk factors of AVN with a large number of patients are needed.