Introduction: High risk of mental health problems is associated with Coronavirus Disease 2019 (COVID-19). This study explored the prevalence of depressive symptoms (depression hereafter) and its relationship with quality of life (QOL) in clinically stable patients with COVID-19. Methods: This was an online survey conducted in COVID-19 patients across five designated isolation hospitals for COVID-19 in Hubei province, China. Depression and QOL were assessed with standardized instruments. Results: A total of 770 participants were included. The prevalence of depression was 43.1% (95%CI: 39.6%-46.6%). Binary logistic regression analysis found that having a family member infected with COVID-19 (OR = 1.51, P = 0.01), suffering from severe COVID-19 infection (OR = 1.67, P = 0.03), male gender (OR=0.53, P < 0.01), and frequent social media use to obtain COVID-19 related information (OR = 0.65, P < 0.01) were independently associated with depression. Patients with depression had lower QOL than those without. Conclusion: Depression is highly prevalent in clinically stable patients with COVID-19. Regular screening and appropriate treatment of depression are urgently warranted for this population.