Background: The first nationwide lockdown due to the COVID-19 pandemic was implemented in Vietnam from April 1 to 15, 2020. Nevertheless, there has been limited information on the impact of COVID-19 on the psychological health of the public. Objective: This study aimed to estimate the prevalence of psychological issues and identify the factors associated with the psychological impact of COVID-19 during the first nationwide lockdown among the general population in Vietnam. Methods: We employed a cross-sectional study design with convenience sampling. A self-administered, online survey was used to collect data and assess psychological distress, depression, anxiety, and stress of participants from April 10 to 15, 2020. The Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety, and Stress Scale-21 (DASS-21) were utilized to assess psychological distress, depression, anxiety, and stress of participants during social distancing due to COVID-19. Associations across factors were explored using regression analysis. Results: A total of 1385 respondents completed the survey. Of this, 35.9% (n=497) experienced psychological distress, as well as depression (n=325, 23.5%), anxiety (n=195, 14.1%), and stress (n=309, 22.3%). Respondents who evaluated their physical health as average had a higher IES-R score (beta coefficient [B]=9.16, 95% CI 6.43 to 11.89), as well as higher depression (B=5.85, 95% CI 4.49 to 7.21), anxiety (B=3.64, 95% CI 2.64 to 4.63), and stress (B=5.19, 95% CI 3.83 to 6.56) scores for DASS-21 than those who rated their health as good or very good. Those who self-reported their health as bad or very bad experienced more severe depression (B=9.57, 95% CI 4.54 to 14.59), anxiety (B=7.24, 95% CI 3.55 to 10.9), and stress (B=10.60, 95% CI 5.56 to 15.65). Unemployment was more likely to be associated with depression (B=3.34, 95% CI 1.68 to 5.01) and stress (B=2.34, 95% CI 0.84 to 3.85). Regarding worries about COVID-19, more than half (n=755, 54.5%) expressed concern for their children aged <18 years, which increased their IES-R score (B=7.81, 95% CI 4.98 to 10.64) and DASS-21 stress score (B=1.75, 95% CI 0.27 to 3.24). The majority of respondents (n=1335, 96.4%) were confident about their doctor's expertise in terms of COVID-19 diagnosis and treatment, which was positively associated with less distress caused by the outbreak (B=-7.84, 95% CI-14.58 to-1.11).