Human papillomavirus (HPV) is the etiological agent of cervical cancer, the second most prevalent neoplasia among women. Although it has been proven that systemic lupus erythematosus (SLE) patients have higher frequency of cervical dysplasia, few studies have focused on HPV prevalence among them. This study aimed to investigate HPV prevalence among SLE patients and to evaluate associated risk factors, including the use of immunosuppressors (IM). Total DNA extracted from cervical samples of 173 SLE patients and 217 women (control group) submitted to routine cervical cytopathology was used as template in polymerase chain reaction (PCR)-based assays for detection of HPV DNA. HPV genotyping was performed by type-specific PCR, PCR-RFLP and/or DNA sequencing. Statistical methods included univariate analysis and logistic regression. Despite presenting significantly fewer HPV risk factors, SLE patients were found to have a threefold increase in HPV infection, mostly genotypes 53, 58, 45, 66, 6, 84, 83, 61, as compared with controls, who presented types 6, 18 and 61 more frequently. The higher rate of HPV infection was associated with immunosuppressive therapy. This study provides evidence that SLE patients have a high prevalence of HPV infection, which is even higher with the use of IM, a condition that might necessitate a more frequent cervical cancer screening program for these women.