A 55-year-old woman with systemic lupus erythematosus was admitted with fever of unknown origin. She had been on an immunosuppressive regimen for the past 8 years including steroids and Azathioprine. Laboratory parameters revealed a markedly elevated C-reactive protein of 189 mg/l, antinuclear antibodies of 1:2,560, a hemoglobin level of 9.0 g/dl, and a severe lymphopenia (total lymphocytes 49.4/μl, CD4⁺ cells 2/μl, CD8⁺ cells 7/μl). Neither blood culture samples nor computed tomography and magnetic resonance imaging of the chest and abdomen nor a trans-esophageal echocardiography revealed positive results. A bone marrow biopsy did not show signs of hematologic disease, but revealed a small granuloma rife with acid-fast bacilli, which were later confirmed to be Mycobacterium genavense by gene sequencing. To our knowledge, this is the first case involving M. genavense infection in a patient with systemic lupus erythematosus. In contrast to other reports regarding disseminated M. genavense infection, the patient is still alive and well.