This study investigates the relationship between territorial human influence and decreases in NO2 air pollution during a total COVID-19 lockdown in Metropolitan France. NO2 data from the confinement period and the Human Influence Index (HII) were implemented to address the problem. The relative change in tropospheric NO2 was calculated using Sentinel-5P (TROPOMI) satellite data. Hotspot-Coldspot analysis was performed to examine the change in NO2. Moreover, the novel Human-Influenced Air Pollution Decrease Index (HIAPDI) was developed. Weather bias was investigated by implementing homogeneity analysis with χ2 test. The correlations between variables were tested with the statistical T-test. Likewise, remote observations were validated with data from in-situ monitoring stations. The study showed a strong correlation between the NO2 decrease during April 2020 under confinement measures and HII. The greater the anthropogenic influence, the greater the reduction of NO2 in the regions (R2 = 0.62). The new HIAPDI evidenced the degree of anthropogenic impact on NO2 change. HIAPDI was found to be a reliable measure to determine the correlation between human influence and change in air pollution (R2 = 0.93). It is concluded that the anthropogenic influence is a determining factor in the phenomenon of near-surface NO2 reduction. The implementation of HIAPDI is recommended in the analysis of other polluting gases.