Purpose: This study aims to investigate factors associated with depression during Coronavirus disease 2019 (COVID-19) quarantine. Methods: An online survey was done to assess depression of the individuals living in Seoul, who were under quarantine due to COVID-19 between October and December 2020. A total of 1,139 individuals were included in our analysis. Logistic regression analysis was performed to investigate factors contributing to depression during COVID-19 quarantine. Results: The prevalence of depression among the participants was 8.5% (women 11.1%, men 5.8%). Our regression analyses showed that pre-existing depression, women, perceived support, correct understanding of the rationale for quarantine, and understanding of quarantine instructions were significantly associated with the likelihood of depression during quarantine due to COVID-19. Conclusion The findings suggest that it is necessary to develop and implement a preemptive measure focusing on vulnerable groups such as women or people with pre-existing depression to prevent depression during quarantine. In addition, this study confirmed that active and efficient communication by the health authorities is essential to better understand the purpose and instructions of quarantine, which is also effective in preventing depressive symptoms during quarantine.