The research presented in this article builds upon a phenomenon of new socio-spatial differentiation progressively occurring in the Czech Republic since 1989, with special attention devoted to rural peripheral areas suffering from a long-term loss of population (depopulation). The authors argue that the persistent out-migration predominately of young and educated inhabitants is one of the key processes of the circular causal mechanism that leads to the marginalisation of particular localities and areas. Selective outmigration entails the disappearance of various socio-cultural activities, more precisely social institutions and civic amenities essential to maintaining or increasing the quality of human capital. Consequently, depopulation could have a severe impact on the developmental potential of a locality, and thus could significantly decrease quality of life in certain localities and particularly among certain social groups of the population. The article provides spatial insight into depopulation tendencies at several geographical levels, especially in the fi nal decades of the last century. Alongside a quantitative analysis of migration, the research included a detailed case study of a municipality in the Pacov region and thus also applied qualitative approaches (e.g. Observation, semi-structured interviews with the inhabitants, and local actors). The article discusses the interconnections between specific effects of depopulation (e.g. a deterioration of accessibility by public transport, poor civic amenities) and their impacts on the quality of life in rural peripheral areas in general.