Infection is a major cause of mortality in patients with systemic lupus erythematosus (SLE). This study describes infectious complications in SLE patients and analyzes the risk factors for infection at the time of SLE diagnosis and during the course of SLE in a case-control study. Of 110 patients enrolled, 42 (38%) had at least 1 episode of infectious disease. The incidence of infectious disease was 4.4/100 patient-years (py) with a total follow-up duration of 954 y. In multivariate analysis, independent predictors of infection at the time of SLE diagnosis were an SLE disease activity index (SLEDAI) > 12 (p = 0.01), C3 levels < 90 mg/dl (p = 0.01) and positive anti-ds DNA antibodies (p < 0.01). Frequent flare-ups (p = 0.04) and follow-up duration > or =8 y (p = 0.023) were also significant risk factors for infectious diseases. It is mandatory to closely observe SLE patients with risk factors for developing infectious diseases.