Abstract Issue In Slovenia the big group of over 150 musculoskeletal and connective tissue diseases (MSCTD) constitute a serious public health problem, a major burden on health systems and society as a whole. Patients with these diseases have a poorer quality of life and often retire early. Any early retirement that could have been prevented represents a loss of human capital, which is a major social and economic cost to society. The aim of this study was to analyze the economic burden of the six most common MSCTD in Slovenia for the period from 2020 to 2022, to contribute to a better understanding of this problem and suggest solutions. Methods At the Slovenian National Institute of Public Health, in collaboration with the Faculty of Economics at the University of Ljubljana, we calculated the burden of six most common MSCTD for the period 2020-2022. We used the National Transfer Accounts (NTA) methodology to calculate the indirect costs; direct costs were calculated based on the national routine health data. Results The calculated economic burden of the six most common diagnoses of MSCTD represents 5% of total health expenditure or 0.4% of Slovenian gross domestic product on average. Direct costs amounted to 2% of total health expenditure (hospitalizations 22.5%, costs for medicines 9.3%, first curative visits at the primary level and visits to the outpatient clinic at the secondary level 2.7%). Indirect costs amounted to 3% of total health expenditure. Conclusions Despite the reduced access to the health system due to COVID-19 the economic burden of MSCTD is high in Slovenia and would be significantly higher considering all diagnoses from this group of diseases. The research requires interdisciplinary cooperation between medicine and economics regarding demanding NTA methodology which is innovative in our country. Key messages • One of the main public health priorities in Slovenia should be to raise awareness of MSCTD. • In the light of the aging population prevention activities with focus on MSCTD should be intensified as soon as possible.