The pandemic situation of COVID-19, which affected almost the entire civilized world with its consequences, offered a unique opportunity for analysis of geographical space. In a relatively short period of time, the COVID-19 pandemic became a truly global event with consequences affecting all areas of life. Circumstances with COVID-19, which affected the territory of Slovakia and its regions, represent a sufficient premise for analysis three years after the registration of the first case in Slovakia. The study presents the results of a detailed spatiotemporal analysis of the course of registered cases of COVID-19 in six periods in Slovakia. The aim of the paper was to analyze the development of the number of people infected with the disease COVID-19 in Slovakia. At the level of the districts of Slovakia, using spatial autocorrelation, we identified spatial differences in the disease of COVID-19. Moran’s global autocorrelation index and Moran’s local index were used in the synthesis of knowledge. Spatial analysis of data on the number of infected in the form of spatial autocorrelation analysis was used as a practical sustainable approach to localizing statistically significant areas with high and low positivity. This manifested itself in the monitored area mainly in the form of positive spatial autocorrelation. The selection of data and methods used in this study together with the achieved and presented results can serve as a suitable tool to support decisions in further measures for the future.