The processes of spatial development of different regions are characterized by different features due to regional specificity, which is also formed under the influence of the structure of regional economy. One of its components is socially oriented non-profit organizations (SONPO). The purpose of the research is to conduct a comparative empirical study of the spatial development of SONPO’s in regions of the Urals and Southern Russia, to identify common trends in their spatial development. The research methodology is based on the theory of spatial economy, in particular on the provisions of the territorial and resource approaches to the study of economic area. The research methods are based on the use and interpretation of basic indicators of the economic area abundance. The zone under analysis is the Ural macro-region (within the economic district) and the South of Russia (within the Southern Federal District). As a result of the research, trends in the spatial development of SONPO’s in the economic area of the Urals and the South of Russia were revealed on the basis of parameters of the dynamics of the number of SONPO’s, as well as the satisfaction of demand from SONPO’s services. The conclusion about the importance of the spatial factor of SONPO’s development was made. It was noted that the directions of the impact strengthening of SONPO’s on the regional spatial development may be specific measures and activities written in regional programs to support their development, such as increase of the number of SONPO’s, implementation of socially significant projects, a set of measures helping to overcome the existing barriers and restrictions in the activities of SONPO’s, as well as the intensification of the implementation of municipal programs to support SONPO’s. The results of the research can be used to control the status and effectiveness of SONPO’s activities in the regions, as well as to specify the spatial development policy.