The aims of this study were to describe the clinical features of patients with systemic lupus erythematosus (SLE) who developed cryptococcal infection and ascertain their outcomes when treated with glucocorticoids and immunosuppressive agents in conjunction with long-term maintenance antifungal therapy. Six cases of cryptococcal infection in SLE were reviewed retrospectively. The mean age at the time of infection was 26.3 (11.7) years. Three patients had active SLE and all were receiving glucocorticoids [median prednisone dose of 40 (21.2-60.0) mg/day] at the time of infection diagnosis. Concomitant cytotoxic agents were used in five patients. Meningitis was the most common clinical manifestation (n = 5) and cryptococcemia was found in three cases. The patient, who developed pulmonary cryptococcosis, died from respiratory distress syndrome. All patients received induction anti-fungal therapy with amphotericin B and the five surviving patients switched to oral fluconazole indefinitely as maintenance therapy and none of them has had relapses of cryptococcal infection to last medical evaluation. As SLE patients have intrinsic abnormalities of cell-mediated immunity and receive immunosuppressive therapy, indefinite maintenance therapy with fluconazole is recommended in SLE patients with cryptococcosis.