Background: Depression is a major contributor to disability, yet clinical assessment and research have primarily focused on symptom severity. This study aims to examine associations between self-reported depression and functioning across the International Classification of Functioning, Disability and Health (ICF), while accounting for environmental and personal factors.

Methods: The study analyzed self-reported data from the 2021 Danish “How are you?” survey. Guided by the ICF framework, associations between self-reported depression and functioning were analyzed using logistic regression in a stratified random sample of 48,936 adults aged 25 years and older.

Results: Of the 28,101 respondents included, 3,060 (13%) reported symptoms indicative of depression. Across all ICF components, individuals with self-reported depression reported substantially more disability than those without depression. After adjustment for personal and environmental factors, depression (reference: no depression) remained strongly associated with impairments in body functions and structures, including poor sleep quality (OR 2.94, 95% CI 2.44–3.54), atypical sleep duration (OR 1.27, 95% CI 1.18–1.37), perceived stress (OR 9.75, 95% CI 8.12–11.72), life strain (OR 1.97, 95% CI 1.67–2.33), and loneliness (OR 2.93, 95% CI 2.43–3.52). Depression was also associated with activity limitations and participation restrictions, including requiring assistance with activities of daily living (OR 1.39, 95% CI 1.10–1.74), difficulty engaging with healthcare providers (OR 1.83, 95% CI 1.44–2.32), non-engagement in work or education (OR 1.40, 95% CI 1.10–1.79), and lack of community involvement (1.19, 95% CI 1.03–1.39).

Conclusions: Self-reported depression was associated with widespread disability across psychological, social, and physical domains, underscoring its relevance as a condition with substantial disability. The findings support the utility of ICF for systematically capturing the multidimensional impact of depression at the population level, informing comprehensive assessment and rehabilitation-practice and research.