The objective of this study was to assess the incidence and risk factors of infections in 200 SLE outpatients. All outpatients with active or inactive SLE without infections in the previous month were included. They were assessed every 3 months. Major infections were those requiring hospitalization and parental antibiotic therapy; minor infections required oral or topical therapy. Sociodemographic, disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), therapy and laboratory variables were evaluated. After a follow-up of 22+/-7 months, 65 (32%) patients had infections; 35% of those were major. The most common sites for infection were urinary (26%), skin (23%), systemic (12%), and vaginal (9%). At infection onset, 50 of 65 patients (77%) had disease activity, with a mean SLEDAI score of 6.1. The variables significantly associated with infection in the univariate analyses were the presence of disease activity, SLEDAI score, renal activity, prednisone dose, and IV cyclophosphamide. The only variable associated with infection in the multivariate analyses was a SLEDAI score of 4 or higher. Most infections in SLE outpatients were single, minor, non-life threatening, and associated with disease activity independently of sociodemographic and therapeutic factors.