Using Sentinel-5P data, this study investigated the magnitude of change in the concentration of air pollutants (NO2, HCHO, SO2, O3, CO, and aerosol index) in the air of ten cities and urban areas of the French region of Grand Est as a result of the first lockdown imposed between March 17, 2020 and May 11, 2020. The results showed that the air quality in the urban environments of Grand Est improved significantly compared to the same period in 2019 without lockdown. NO2, O3, aerosol index and CO were the pollutants that exhibited maximum reductions by an average of -33.98%, -5.94%, -26.82% and -0.66%, respectively (the observed maximum decreases were -54.7%, -7.7%, -13.1%, and -5.3%, respectively). The largest decrease occurred in the Public Establishments of Inter-municipal Cooperation (EPCI, in French: Établissement public de coopération intercommunale) areas of Eurométropole de Strasbourg, CA Colmar, and CA Mulhouse Alsace. The maximum decrease in air pollution first occurred in land cover classes close to cities, followed by built-up urban areas. In this study, a global depollution index known as the atmospheric clearance index (ACI) was developed, which involved several air pollution parameters, and quantitatively analyzed the decrease in contamination levels of the atmosphere in this region. In addition, the correlation between the novel ACI and other population and economic development indices was studied. The results indicated that there was a negative and statistically significant correlation between ACI and population density, gross domestic product, gross value added (GVA) at basic prices, number of employees, and active enterprises.