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Coexisting systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection cases are rare worldwide. Great challenges are posed on the diagnosis and treatment of such concurrent cases.We report the case of a 44-year-old Chinese man with edema, hematuria, and fever who presented at West China Hospital, Sichuan University, Chengdu, Sichuan, China, in 2013.An initial diagnosis of SLE was made from the clinical manifestations and laboratory findings based on the Systemic Lupus International Collaborating Clinics classification criteria. Immunosuppressant therapy relieved him of the edema and hematuria, but he regained the symptoms after a cold. Workup, including electrochemiluminescence immunoassay, western blot, and polymerase chain reaction analysis, revealed that he was concurrently infected with HIV after hospitalization.The treatment plan included methylprednisolone and cyclophosphamide, with gastroprotective and hepatoprotective agents, simultaneously aiming to reduce urinary protein. After HIV infection confirmed, cyclophosphamide was stopped. He was referred to the local Centers for Disease Control and Prevention for combination antiretroviral therapy (ART). He was suggested to continue monitoring CD4 T-cell count for an appropriate dose of immunosuppressive drugs.In the last follow-up in May 2017, he had been stable in terms of both SLE and HIV infection.The case highlights the presence of concurrent SLE and HIV infection. Laboratory technicians and clinicians should be cautious on diagnosis, especially in eliminating the false-positive results. Attention should be paid to the dose of immunosuppressants and the ART procedure.