The spread of the COVID-19 had profoundly affected the development of the air transportation. In order to determine the changes in air transportation volume associated with the development of the epidemic, this paper takes Southwest China as the study area. Monthly data and methods, such as the coefficient of variation, rank-size analysis and spatial matching index, were applied. The results found that: (1) during 2020–2022, there was a positive relationship between passenger volume and epidemic development, while freight volume increased for most airports in the first quarter of 2020–2022, particularly in the eastern region; (2) From the perspective of changes in air transportation volume under the development of the COVID-19, among various types of airports, the changes in transportation volume of main trunk airports were more significant than those of regional feeder airports in remote areas; (3) however, under the influence of the epidemic, main trunk airports still exhibited stronger attraction in passenger volume. That is to say, the passengers who chose to travel by air still tended to choose the main trunk airports and formed the agglomeration distribution pattern which around high-level airports in the provincial capital. Whereas the freight volume had a tendency of equalization among airports in Southwest China; (4) Over the course of time, the consistency of the spatial distribution of the number of cases and the passenger or freight volume in southwest China gradually increased. Among them, the spatial matching rate of the passenger volume and the number of COVID-19 cases was always higher than that of the cases and freight volume, which might indicate that there was a stronger correlation relationship. Therefore, it is proposed that the construction of multi-center airport system should be strengthened, the resilience of the route network for passenger transportation should be moderately enhanced, and the risk-resistant capacity of mainline airports and airports in tourist cities should be upgraded, so as to provide references for the orderly recovery of civil aviation and regional development.