BACKGROUND: This study aimed to investigate factors related to high stress levels among the general population in China during the novel coronavirus disease (COVID-19) pandemic when its containment measures were in place and to identify the most stressed populations. METHODS: A nationwide study was conducted online among 5,039 adults in all 31 provinces in mainland China between March 1 and March 16, 2020. Bivariate analysis and multivariate logistic regressions were performed to explore the related factors of high perceived stress. RESULTS: Among all respondents, 36.0% reported a high level of stress. Respondents in Hubei province (the epicenter) were more likely to report high stress levels than those in low epidemic areas. Respondents who went outside every day or every other day reported greater odds of experiencing a high level of stress than those who went outside every 8-14 days. People with higher risk perceptions were more prone to report high stress levels. Respondents aged 16-35 were more likely to report high stress than respondents aged 46 or older. Lower household income and lower health literacy were related to increased odds of reporting high stress levels. LIMITATIONS: We used a convenience sample and self-reported survey data. CONCLUSIONS: We identified risk factors for high stress levels related to the epidemic (epidemic intensity in residential areas, risk perception, and frequency of going outside) and other vulnerabilities (younger age, low household income, low health literacy). Our findings can directly inform interventions and policies for mitigating stress among the general population for this or future epidemics.