Despite frequent pleuro-pulmonary involvement, spontaneous pneumothorax is rare in patients with systemic lupus erythematosus (SLE). Here, we report a 17-year-old female patient with SLE, complicated by multiple organs involvement. She initially presented with interstitial pneumonitis and pulmonary hemorrhage, followed by spontaneous pneumothorax and CNS involvement. The patient was treated with immunosuppressive agents, including steroid and cyclophosphamide pulse therapies. Spontaneous pneumothorax happened to her once again at a different location during treatment. After aggressive therapy, the disease activity of SLE gradually diminished, and pneumothorax had not recurred during the further follow-up. Therefore, the pneumothorax may occur in SLE patients with high disease activity.