Cryptococcal infection is a rare, yet well recognized complication of systemic lupus erythematosus (SLE). We present a case of mesenteric and retroperitoneal cryptococcal lymphadenitis resulting in the obstruction of the stomach and proximal duodenum in a patient suffering from SLE, while recently she did not receive any immunosuppressive treatment. A 42-yr-old woman was admitted due to high fever and diffuse abdominal pain for three weeks. Abdominal computed tomography (CT) scan showed multiple conglomerated lymphadenopathies in the retroperitoneum and the mesentery resulting in luminal narrowing of the third portion of the duodenum. Cryptococcal lymphadenitis was proven by needle biopsy and she was treated with intravenous liposomal amphotericin B, followed by oral fluconazole. After fourteen-month antifungal therapies, the clinical symptoms and follow-up images improved. This case emphasize that the intrinsic immunological defects of SLE may be directly responsible for the predisposition to fungal infections.