This paper analyses the uneven geography of the COVID-19 health impact in OECD and European countries. It first describes the increase in all-cause mortality – i.e. excess mortality – across subnational regions between January and December 2020. Subsequently, it investigates the regional factors associated with higher excess mortality, looking at demographic, socio-economic, institutional and environmental features of regions. Results show that excess mortality has a significant spatial dimension, with the hardest hit regions having excess mortality rates that were, on average, 17 percentage points higher than the least affected regions in the same country. During the first year of the pandemic, lower health system capacity, followed by population density, air pollution, share of elderly population and lower institutional quality were associated with higher excess mortality. While health system capacity and population density have been strongly associated to excess mortality throughout the COVID-19 crisis, trust in government and air pollution showed stronger correlations with excess mortality in the later phases of the pandemic. Finally, prolonged remote working, particularly after two-months, is also associated with lower excess mortality.