Introduction: Adherence to COVID-19 preventative guidelines may be influenced by a variety of factors at the individual, societal, and institutional levels. The current study sought to investigate the social factors of adherence to those preventive measures from the perspective of health professionals., Methods: In October 2020, we performed qualitative research in Tehran, Iran, using the directed content analysis method. For the preparation of our interview guide and data analysis, we employed the WHO conceptual framework of socioeconomic determinants of health. Semi-structured interviews were conducted with 15 health professionals and policymakers who were chosen using a purposive sampling approach. MAXQDA-18 software was used to analyze the data. The Goba and Lincoln criteria were used to assess the quality of the results., Results: There are 23 subcategories and 9 categories, which include socio-economic and political context (unstable macroeconomic environment, poor management of the pandemic, media and knowledge transfer), cultural and social values (fatalism, cultural norms, value conflicts, social customs), socio-economic positions (livelihood conditions), social capital (social cohesion, low trust), living conditions (housing conditions), occupational conditions (precarious employment), individual characteristics (demographic characteristics, personality traits, COVID-19 knowledge, and attitude), psycho-social factors (normalization of the disease, social pressure, and stigma), and health system leadership (health system problems, not taking evidence-based decisions, non-comprehensive preventive guidelines, non-operational guidelines, inadequate executive committee) were obtained., Conclusion: To limit the new COVID-19 transmission, people must be encouraged to follow COVID-19 prevention instructions. Improving adherence to COVID-19 preventive guidelines necessitates dealing with the complexities of responding to social determinants of those guidelines. Increasing public health literacy and knowledge of COVID-19, informing people about the consequences of social interactions and cultural customs in the spread of COVID-19, strengthening regulatory lockdown laws, improving guarantees for adhering to preventive guidelines, providing easy access to preventive supplies, and strengthening financial support for households with precarious employment are all important.