The COVID-19 pandemic has greatly affected public health and wellbeing. In response to the pandemic threat of the coronavirus epidemic, several countries, including China, adopted lockdown and quarantine policies, which may cause psychological distress. This study aimed to explore the psychological impact of province-wide lockdown and personal quarantine during the COVID-19 outbreak in China as well as the corresponding risk factors and protective factors. We examined the immediate (2-week) and delayed (2-month) impact of province-wide lockdown and personal quarantine on psychological distress in a national sample of 1390 Chinese residents. No immediate impact of province-wide lockdown on psychological distress was observed, whereas personal quarantine increased individuals' anxiety, fear, and anger. Despite the lack of initial association, psychological distress increased among those in province-wide lockdown. Self-stigma and personal control both significantly moderated the association between lockdown and psychological distress, but in different directions. Those with higher self-stigma and lower personal control were more impacted by the lockdown. Government support moderated the impact of quarantine on psychological distress, but not that of lockdown. The delayed effects of lockdown and quarantine on psychological distress were observed, and self-stigma, social support, and perceived control moderate the relationships. This study is the first to demonstrate the psychological costs of province-wide lockdowns on individuals' mental health, providing evidence of the need for mitigation strategies and timely public mental health preparedness in countries with recent outbreaks of COVID-19.