Since 2014, the problem of sanctions and counter-sanctions has not left the front pages of popular and scientific publications and most information resources. A large number of works by domestic and foreign authors, consulting agencies gave both positive and negative forecasts of the impact of anti-Russian sanctions on the country’s economy as a whole. Over the course of 8 years, various types of sanctions were introduced that dealt an economic blow to both individuals and sectors of the economy and specific corporations that are represented in different regions of the country, which undoubtedly carries risks for the socio-economic security of the constituent entities of the Russian Federation. The subjects of the Russian Federation have a different structure of the economy and the level of socio-economic development, while the impact of sanctions on the level of socio-economic security of individual regions and the possibilities of leveling them have not yet been sufficiently investigated, which gives this topic high relevance. The purpose of the study is to assess the nature of the sanctions and their impact on the socio-economic security of the regions. The work uses bibliographic, analytical, statistical and mathematical research methods, analyzes open statistical data in the context of the regions of the Volga Federal District (VFD). As a result of the study, an analysis of the degree of influence of sanctions pressure on the indicators of foreign trade operations, the availability of technologies, the level of overdue loans, and the financial results of companies’ activities was presented. As a result of the study, factors were identified that have a greater impact on the state of the regional economy, indicators, indicators and directions for reducing the impact of sanctions on the socio-economic security of the Volga Federal District regions.