Background <p>Social isolation and withdrawal, particularly among young people, have become significant social issues, raising concerns about mental health disorders. This study explores the association between social isolation, withdrawal, and depressive symptoms in young adults, focusing on sex differences and underlying factors.</p> Methods <p>Data from 5,513 participants in the Seoul Government Survey on Socially Isolated and Withdrawn Young Adults were included in this study. Social isolation and withdrawal were measured based on levels of emotional or physical isolation and the amount of time spent at home instead of attending work or school. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9) scale. Multiple and multinomial logistic regression analyses were performed to investigate the associations between social isolation, withdrawal, and depression.</p> Results <p>Socially isolated young adults demonstrated a strong association with depression (isolation only: Male, odds ratio [OR] 2.06, 95% confidence interval [CI] 1.38–3.08; Female, OR 2.95, 95% CI 2.06–4.95; isolation including withdrawal: Male, OR 2.56, 95% CI 1.11–5.89; Female, OR 2.40, 95% CI 1.04–5.57). However, withdrawal alone did not show any significant association. As depressive symptoms intensified (PHQ-9 ≥ 20), the association with social isolation strengthened (Male, OR 6.50, 95% CI 3.23–13.08; Female, OR 6.82, 95% CI 3.43–13.58). Prolonged isolation (≥ 3 years) was strongly associated with depression (Male, OR 2.91, 95% CI 1.76–4.79; Female, OR 6.04, 95% CI 3.58–10.20).</p> Conclusion <p>Among young adults, the association between social isolation and depression intensifies with prolonged isolation and increased symptom severity, while withdrawal alone has no such effect. This highlights the importance of addressing social isolation and related issues in mental health interventions for young adults.</p>