Through a weekly all-cause mortality surveillance system, we observed in France a major all-cause excess mortality from March to May 2020, concomitant with the coronavirus disease (COVID-19) epidemic. The excess mortality was 25,030 deaths, mainly among elderly people. Five metropolitan regions were the most affected, particularly Île-de-France and the Grand-Est regions. Assessing the excess mortality related to COVID-19 is complex because of the potential protective effect of the lockdown period on other causes of mortality.