We analysed the interplay between palmiped farm density and the vulnerability of the poultry production system to highly pathogenic avian influenza (HPAI) H5N8. To do so, we used a spatially-explicit transmission model, which was calibrated to reproduce the observed spatio-temporal distribution of outbreaks in France during the 2016–2017 epidemic of HPAI. Six scenarios were investigated, in which the density of palmiped farms was decreased in the municipalities with the highest palmiped farm density. For each of the six scenarios, we first calculated the spatial distribution of the basic reproduction number (R0), i.e.the expected number of farms a particular farm would be likely to infect, should all other farms be susceptible. We also ran in silico simulations of the adjusted model for each scenario to estimate epidemic sizes and time-varying effective reproduction numbers. We showed that reducing palmiped farm density in the densest municipalities decreased substantially the size of the areas with highR0values (> 1.5). In silico simulations suggested that reducing palmiped farm density, even slightly, in the densest municipalities was expected to decrease substantially the number of affected poultry farms and therefore provide benefits to the poultry sector as a whole. However, they also suggest that it would not have been sufficient, even in combination with the intervention measures implemented during the 2016–2017 epidemic, to completely prevent the virus from spreading. Therefore, the effectiveness of alternative structural preventive approaches now needs to be assessed, including flock size reduction and targeted vaccination.