Bartonella quintana infections have recently been reported in homeless patients. We prospectively studied the prevalence of and the factors associated with a positive serology to B quintana in the homeless population of downtown Paris. The following data were recorded: ongoing cutaneous parasitic infestation, years of homelessness, living status, previous episodes of body pediculosis and scabies, alcoholism, intravenous drug use, known immunodepression (including undernutrition and known HIV infection), and contacts with animals. B quintana serology was performed in 57 patients and in 53 age- and sex-frequency-matched downtown Paris volunteer blood donors. Thirty-one patients (54%; 95% confidence interval [CI], 41%-68%) had a positive B quintana serology as compared with 2% in the control group (P <.0001); 8 of 57 patients (14%; 95% CI: 6%-26%) had a serologic profile of an evolving infection. Age and years of homelessness were independently associated with a positive B quintana serology with adjusted relative risks (RRs) of 2.9 (95% CI, 1.4-5.9) for age 40 years and older and 1.7 (95% CI, 1.1-2.7) for years of homelessness 3 or more. Our results suggest a high prevalence of past and recent infections with B quintana in the downtown Paris homeless population with cutaneous parasitic infestations.