BACKGROUND: Self-protective behaviors of social distancing and vaccination uptake vary by demographics and affect the transmission dynamics of influenza in the United States. By incorporating the socio-behavioral differences in social distancing and vaccination uptake into mathematical models of influenza transmission dynamics, we can improve our estimates of epidemic outcomes. In this study we analyze the impact of demographic disparities in social distancing and vaccination on influenza epidemics in urban and rural regions of the United States. METHODS: We conducted a survey of a nationally representative sample of US adults to collect data on their self-protective behaviors, including social distancing and vaccination to protect themselves from influenza infection. We incorporated this data in an agent-based model to simulate the transmission dynamics of influenza in the urban region of Miami Dade county in Florida and the rural region of Montgomery county in Virginia. RESULTS: We compare epidemic scenarios wherein the social distancing and vaccination behaviors are uniform versus non-uniform across different demographic subpopulations. We infer that a uniform compliance of social distancing and vaccination uptake among different demographic subpopulations underestimates the severity of the epidemic in comparison to differentiated compliance among different demographic subpopulations. This result holds for both urban and rural regions. CONCLUSIONS: By taking into account the behavioral differences in social distancing and vaccination uptake among different demographic subpopulations in analysis of influenza epidemics, we provide improved estimates of epidemic outcomes that can assist in improved public health interventions for prevention and control of influenza.