Introduction. In the Russian Federation, there is a significant differentiation in mortality rates both between regions and within individual subjects. Mortality rates and life expectancy characterize the health status and quality of life of the population; their analysis allowed us to assess various aspects of society, such as economic development, level and organization of healthcare. Life expectancy at birth is an integral indicator that reflects mortality in different age groups. Reducing the mortality rate and increasing life expectancy at birth are priority tasks for Russia at present. The goal is to analyze the age and sex characteristics of mortality and life expectancy at birth among the urban and rural population of the Orenburg region. Materials and methods. For the analysis, consolidated reports of the State Budgetary Healthcare Institution of the Orenburg Region "Medical Information and Analytical Center" were taken. The study period is from 2000 to 2023. Data on COVID-19 were taken from the information resources of the Ministry of Health of the Russian Federation for monitoring the epidemiological situation on COVID-19. The population according to the territorial body of the Federal State Statistics Service for the Orenburg Region as of January 1, 2024 in the Orenburg Region was 1,828,656 people. The statistical method was used in the work. Mortality rates are calculated per 1000 population. Results and discussions. As of January 1, 2024, the Orenburg region has a population of 1,828,656 people, the settlement density is 14.8 inhabitants per 1 sq.m. It includes 12 cities of regional subordination, 35 districts, 1708 rural settlements. The share of urban population is 60%, the share of rural - 40%, while in the Russian Federation, according to Rosstat data as of 01.01.2024, the share of urban residents is 75%, the share of rural - 25%[7,8]. From 2005 to 2019, there has been a significant increase in life expectancy at birth both in the country as a whole and in the Orenburg region. A characteristic feature of the demographic situation in Russia is a significant difference between the life expectancy of women and men, in the Orenburg region the differences are 12 years. From 2004 to 2019, the dynamics of mortality rates are characterized by a positive trend towards a decrease in the mortality rate. And in 2020, the overall mortality rate increased by 23.7%. A 6.6-fold decrease in the mortality rate from the new coronavirus infection Covid-19 in 2022 compared to 2021 provoked a 29.3% decrease in mortality rates from all causes and an increase in life expectancy to 71.27 years. Conclusion (findings). The analysis of the indicators showed the heterogeneity of problems across municipalities, which requires a differentiated approach to assessing processes and developing appropriate regional policy measures. It is necessary to regularly monitor mortality rates and analyze the causes of differences between and within regions. Creation of programs aimed at improving living conditions and access to medical care in regions with high mortality rates. Inclusion in programs of measures to improve the quality of life, develop infrastructure and support healthcare.