ObjectivesWe observed the prevalence and distribution of potential risk factors for sexually transmitted infections (STIs) among Marseille homeless population. MethodsOver the 2000-2015 period, we enrolled 1890 sheltered homeless adults and collected serum samples. Markers of hepatitis B and C viruses (HBV, HCV) and Treponema pallidum were searched using the CMIA testing. Positive HBsAg or anti-HCV samples underwent sequencing; positive anti-T. pallidum sera were subjected to the RPR test. ResultsThe overall prevalence of HBsAg, anti-HBs, anti-HBc, anti-HCV and anti-T. pallidum (by CMIA and RPR) was 4.1%, 22.9%, 35.5%, 5.3% and (6.8%, 1.0%), respectively. We found a significantly higher prevalence of HBsAg and anti-T. pallidum among individuals born in sub-Saharan Africa (or Asia) compared to those born in Europe. Being older (>42 years), toxicomania status, cannabis use and underweight status (compared to normal status) were independent factors associated with HCV seropositivity. Using sequencing, we obtained a substantial diversity of HBV and HCV genotypes. One HCV sequence harbouring a L31M substitution in the NS5a protein may be associated with reduced drug sensitivity. ConclusionsThe positive relationship between toxicomania and HCV suggests the need for effective prevention programmes including health education activities and addiction treatment.