Genital infection by human papillomavirus (HPV) tends to occur more frequently in patients with conditions associated with immune suppression. Systemic lupus erythematosus (SLE) is an immunological disorder characterized by generalized inflammation and a number of clinical manifestations and circulating autoantibodies. The aim of the present study was to determine the prevalence of genital HPV infection among female SLE patients. Women diagnosed with SLE based on American College of Rheumatology classification criteria followed at rheumatology outpatient clinic of the Escola Bahiana de Medicina e Saude Publica, Salvador, Brazil, were included in the study. As a comparison group, clinically healthy women who were attending the gynecology outpatient clinic for routine examination at the same institution were recruited. Testing for cervical HPV infection was performed using the nested polymerase chain reaction technique. Eighty-eight female SLE patients (mean age, 41.4 ± 11.6 years) and seventy healthy female subjects (control group) were studied. The prevalence of HPV infection was 80.7 % (71/88) in the SLE group and 35.7 % (25/70) in the control group (p < 0.0001). After adjustment of the variables (early sexual activity, number of partners and obstetric history), the odds ratio (OR) for genital HPV infection in women with SLE was 7.2 (95 % CI, 2.9 to 17.8; p = 0.0001). The use of immunosuppressive drugs was not associated with a higher prevalence of HPV infection. This study demonstrated that SLE patients have a higher prevalence of genital HPV infection, even when exposed to less potential risk factors for the virus.