Due to the long-term demographic depopulation of settlements, depopulation clusters are observed in Serbia after the 2022 census - areas with 20 or fewer inhabitants or without inhabitants. The areas of depopulated settlements are growing territorially and continue to increase from south towards the North of the country. While the built-up area on the left is expanding around the large cities and around the main roads in Serbia, geographically and functionally isolated villages and smaller towns are being covered by natural vegetation. Even in urban areas, there is a polarisation of highly desirable and sought-after space and undesirable space in a very small area, which is reminiscent of similar phenomena in other countries. In view of population decline, the management of natural resources at all levels of planning and administration is one of the most important issues in spatial planning. In this paper, changes in vegetation cover in depopulated clusters were analysed based on time series data and a formal database of natural resources of depopulated municipalities. It also analysed the correlation of several factors linking population decline to environmental changes. The aim of the work is to determine the natural potential of depopulation clusters in the areas of arable land, mineral resources, renewable energy sources, thermo-mineral sources and forest funds, as well as the way they are currently managed.