Background: Tick-borne diseases are a serious threat to the epidemiological safety of the population of the Stavropol Region, making up more than 70 per cent of all natural focal infectious diseases registered in this territory annually. A wide range of hosts contributes to high tick abundance, diversity of tick-borne pathogens, and maintenance of the natural foci. Objective: To assess the activity of natural foci of tick-borne infections in the Stavropol Region in 2016–2020. Materials and methods: We used notifications submitted by the Center for Hygiene and Epidemiology in the Stavropol Region to the Scientific and Methodological Center for Monitoring the Pathogens of Infectious and Parasitic Diseases of Pathogenicity Groups II–IV for the subjects of the North Caucasian and Southern Federal Districts and the results of an epizootological survey of the Stavropol territory by specialists of the Stavropol Plague Control Research Institute. Markers of the causative agents of tick-borne diseases were detected by ELISA and PCR methods. Data processing was carried out using Microsoft Excel 2010. Results: Active natural foci of Crimean-Congo hemorrhagic fever, Q fever, a group of tick-borne spotted fevers, Lyme disease, human granulocytic anaplasmosis, and human monocytic ehrlichiosis were established in the region in 2016–2020. Human cases of the Crimean-Congo hemorrhagic fever, Lyme borreliosis and Q fever were also registered annually. The abundance of infected ticks in resort towns of the Caucasian Mineral Waters is of particular concern. Conclusion: We established up-to-date epizootic and epidemic manifestations of tick-borne infections in the Stavropol Region in the modern period, which are an important link in epidemiological surveillance and the basis for improving preventive measures