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The innovative development of the region ensures its long-term competitiveness. The aim of the study is to determine the impact of COVID-19 on the development of RIS based on the PESTEL analysis method. The following research methods were used: the PESTEL analysis method and a qualitative research method, which consists in forming a model of the influence of the factors of the COVID-19 pandemic on the RIS. The article analyzes the regional innovation system, identifies the factors reflecting the efficiency of its activities, which are divided into three groups: resources for creating knowledge and technologies; the result of the creation of knowledge and technology; and the commercialization of knowledge and technology. On the basis of the PESTEL analysis method, a diagram of the environment of the regional innovation system is constructed in the context of the following groups of factors: political, economic, socio-cultural, technological, environmental and legal. The dependence of the regional innovation system on these groups of factors is described. The key areas of potential impact of the COVID-19 pandemic on the regional innovation system are identified, the most important factors determining the indirect impact are identified. The results of this article will allow further cross-analysis between quantitative indicators of the two groups to determine updated estimates of the impact of the COVID-19 pandemic on RIS and predict the possible development of RIS within several years after the end of the COVID-19 pandemic, taking into account the characteristics of specific regions.