The research aims to study the qualitative characteristics of the regional economic space and the significance of their changes during a period of uncertainty. The research objectives are (1) to justify the choice of indicators for assessing the quality of the economic space in the region, (2) to analyze changes in the economic space of the Russian regions from 2019 to 2021, and (3) to define measures for improving the quality of the economic space in the region. The author’s approach makes it possible to assess the quality of the economic space in the region based on the calculation of several indicators: the density of economic objects, the intensity of connections between them, the uniformity of the placement of objects, and the organization of economic activity in the region. The results allowed the authors to group the federal districts of Russia according to the quality of the economic space to improve regional management. The proposed methodology made it possible to assess the impact of the COVID-19 pandemic on regional economies in the context of their spatial development. The authors presented an alternative approach to assessing the effectiveness of spatial development of regions. Conducting a study based on this approach makes it possible to obtain results that differ from the results of a quantitative analysis of regional development. The research proposes measures to optimize the development of regions with medium and low levels of economic space quality.