BACKGROUND: Armed conflict erupted in eastern Ukraine in 2014 and still continues. This conflict has resulted in an intensification of poverty, displacement and migration, and has weakened the local health system. Ukraine has some of the highest rates of HIV and Hepatitis C (HCV) in Europe. Whether and how the current conflict, and its consequences, will lead to changes in the HIV and HCV epidemic in Ukraine is unclear. Our study aims to characterize how the armed conflict in eastern Ukraine and its consequences influence the pattern, practice, and experience of sex work and how this affects HIV and HCV rates among female sex workers (FSWs) and their clients. METHODS: We are implementing a 5-year mixed methods study in Dnipro, eastern Ukraine. Serial mapping and size estimation of FSWs and clients will be conducted followed by bio-behavioral cross-sectional surveys among FSWs and their clients. The qualitative component of the study will include in-depth interviews with FSWs and other key stakeholders and participant diaries will be implemented with FSWs. We will also conduct an archival review over the course of the project. Finally, we will use these data to develop and structure a mathematical model with which to estimate the potential influence of changes due to conflict on the trajectory of HIV and HCV epidemics among FSW and clients. DISCUSSION: The limited data that exists on the effect of conflict on disease transmission provides mixed results. Our study will provide rigorous, timely and context-specific data on HIV and HCV transmission in the setting of conflict. This information can be used to inform the design and delivery of HIV and HCV prevention and care services.