Background: Mobility is an important risk determinant for HIV given the potential for intermittent access to HIV services. Mobility may be particularly relevant among female sex workers, (FSW) who have been shown to be at high risk for HIV in settings around the world. Data regarding the role mobility plays in exacerbating HIV risks among FSW across Sub-Saharan Africa remains limited, and data on FSW in Guinea-Bissau is sparse.Methods: FSW in four regions of Guinea-Bissau were recruited with a respondent-driven sampling (RDS) method and participated in an integrated bio-behavioral survey. Associations between reported mobility and social and HIV vulnerabilities among FSW in Guinea-Bissau were assessed using multivariable logistic regression models. Results: 34.8% of respondents reported mobility to one location and 15.7% reported mobility to more than one location within the past six months. Statistical analysis demonstrated that mobility to more than one destination was significantly associated with recent sex without a condom with both clients (aOR: 2.57 (95% CI: 1.10, 6.00)) and non-paying partners (aOR: 4.73 (95% CI: 2.24, 10.02)) compared to non-mobility. However, mobility to one or more locations was also associated with higher odds of receiving HIV prevention information (mobility to one location: aOR: 1.63 (95% CI: 1.07, 2.49); mobility to >1 location: aOR: 2.34 (95% CI: 1.28,4.26)) and mobility to more than one location was associated with more engagement with HIV-related organizations (aOR: 2.26 (95% CI: 1.27, 4.04)).Conclusions: These results suggest that while some prevention services including HIV prevention information reach mobile FSW in Guinea-Bissau, HIV prevention needs remain unmet for mobile FSW in Guinea-Bissau.