Background: The first wave of the COVID-19 pandemic in France was associated with high excess mortality, and anecdotal evidence pointed to differing excess mortality patterns depending on social and environmental determinants. In this study we aimed to investigate the spatial distribution of excess mortality during the first wave of the COVID-19 pandemic in France and relate it at the subnational level to contextual determinants from various dimensions (socioeconomic, population density, overall health status, healthcare access etc.). We also explored whether the determinants identified at the national level varied depending on geographical location. Methods: We used available national data on deaths in France to calculate excess mortality by department for three age groups: 0-49, 50-74 and > 74 yrs. between March 1st and April 27th, 2020. We selected 15 variables at the department level that represent four dimensions that may be related to overall mortality at the ecological level, two representing population-level vulnerabilities (morbidity, social deprivation) and two representing environmental-level vulnerabilities (primary healthcare supply, urbanization). We modelled excess mortality by age group for our contextual variables at the department level. We conducted both a global (i.e., country-wide) analysis and a multiscale geographically weighted regression (MGWR) model to account for the spatial variations in excess mortality. Results: In both age groups, excess all-cause mortality was significantly higher in departments where urbanization was higher (50-74 yrs.: β = 15.33, p < 0.001; > 74 yrs.: β = 18.24, p < 0.001) and the supply of primary healthcare providers lower (50-74 yrs.: β = − 8.10, p < 0.001; > 74 yrs.: β = − 8.27, p < 0.001). In the 50-74 yrs. age group, excess mortality was negatively associated with the supply of pharmacists (β = − 3.70, p < 0.02) and positively associated with workrelated mobility (β = 4.62, p < 0.003); in the > 74 yrs. age group our measures of deprivation (β = 15.46, p < 0.05) and morbidity (β = 0.79, p < 0.008) were associated with excess mortality. Associations between excess mortality and contextual variables varied significantly across departments for both age groups. Conclusions: Public health strategies aiming at mitigating the effects of future epidemics should consider all dimensions involved to develop efficient and locally tailored policies within the context of an evolving, socially and spatially complex situation.