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The chapter aims to determine the impact of the COVID-19 pandemic and crisis on e-business in Industry 4.0. Dynamic modeling by regression and trend analysis methods found that e-business in Industry 4.0 showed a decline in the COVID-19 pandemic and crisis. The regression analysis method reveals that doing e-business in Industry 4.0 in the COVID-19 pandemic and crisis environment is determined by the demand of information society and the factors of telecommunication infrastructure, the management of which allows supporting e-business in Industry 4.0 in these conditions. The contribution of this research to the literature lies in the development of scientific positions of e-business theory by clarifying the effects of the COVID-19 pandemic and crisis on doing e-business in Industry 4.0, as well as identifying the managerial apparatus for mitigating these effects.