Assessment of regional variation in the COVID-19 epidemic is an important task for the implementation of effective action in public health, especially in densely populated regions. In this descriptive study, the temporal and spatial variability of morbidity and in-hospital mortality of COVID-19 in the Silesian Voivodship (Poland) was analyzed. Secondary epidemiological data of hospitalized patients due to COVID-19 from 1 March to 31 December 2020 and from 1 January to 31 December 2021 were obtained from the regional registry of the Silesian Voivodship Office in Katowice. A year by year (2020 versus 2021) comparative analysis showed a similar course pattern of the COVID-19 pandemic in the Silesian Voivodeship; with the worst situation occurring in the colder months of the year. The percentage of in-hospital mortality remained at a high level, close to 20% during the second year of observation. The risk of death in patients hospitalized due to COVID-19 increased with the number of comorbidities. The highest number of patients was documented in densely inhabited regions with intensive population movement (Częstochowa and border counties). The epidemiological ‘map’ facilitates the generation of hypotheses needed for the explanation of the observed epidemic hazard in one of the most populated regions of Poland.