Today, in an unstable international political situation, the urgent issue of ensuring national and regional economic security is more urgent than ever. Ensuring the stability of indicators of economic processes is to develop and improve a flexible system of protection measures against adverse external and internal factors and threats. It is the minimization of the impact of threats, as well as ensuring the stability and security of the economy in critical conditions that constitutes the essence of economic security. Based on objective and subjective factors, the subjects of the Russian Federation differ significantly in the level of socio-economic development and, as a result, in the level of economic security. Such a spread cannot but affect the level of security of the entire state. Regional specifics must necessarily be applied when assessing threats to economic security at the country level. In 2019–2020, the COVID pandemic significantly affected the state of not only regional, but also national economic security. The measures taken by the Government of the Russian Federation to stabilize the economic situation had a positive effect, but cost significant additional costs to both federal and regional budgets. Despite government support for business, there was a decline in the quality of life in the country, an increase in unemployment due to the reduction of staff by many enterprises, a reduction in workers' wages and other socio-economic phenomena that we consider as sources of risks and threats to economic security. As part of the study, an analysis of the state of economic security of the Voronezh region was carried out, threats to its economic security were identified and assessed. The state of economic security of the region in the period under study was negatively affected by: a significant increase in inflation against the background of the global crisis in 2020, a decrease in the share of investments in fixed assets, a drop in the index of industrial production, a drop in innovation activity, an increase in social tension. At the same time, the retail trade turnover per capita was marked by positive dynamics, the share of citizens with incomes below the subsistence minimum decreased, and the gross regional product grew. Among the threats to the economic security of the region, the most dangerous are: the increase in prices for goods and services, the slowdown in the growth of innovation and investment activity, the deterioration of the social sphere.