Introduction: Coronavirus disease 2019 (COVID-19) has significantly affected health care workers (HCWs), including their mental health. However, there has been limited evidence on this topic in the Vietnamese context. Therefore, this study aimed to explore COVID-19-related, psychological stress risk factors among HCWs, their concerns and demands for mental health support during the pandemic period.Methods: We employed a cross-sectional study design with convenience sampling. An online, self-administered questionnaire was used and distributed through social media among medical and non-medical HCWs from April 22 to May 12, 2020. HCWs were categorized either as frontline or non-frontline. We measured the prevalence of psychological stress using the Impact of Event Scale-Revised (IES-R) instrument. Multivariate binary logistic regression analysis was performed to identify risk factors associated with psychological stress among HCWs.Results: Among the 774 enrolled participants, 761 (98.3%) eligible subjects were included in the analysis. Most respondents were females (58.2%), between 31 and 40 years of age (37.1%), lived in areas where confirmed COVID-19 cases had been reported (61.9%), medical HCWs (59.9%) and practiced being at the frontline (46.3%). The prevalence of stress was 34.3%. We identified significant risk factors such as being frontline HCWs (odds ratio [OR] = 1.77 [95% confidence interval [CI]: 1.17–2.67]), perceiving worse well-being as compared to those before the COVID-19 outbreak [OR = 4.06 (95% CI: 2.15–7.67)], and experiencing chronic diseases [OR = 1.67 (95% CI: (1.01–2.77)]. Majority (73.9%) were concerned about testing positive for COVID-19 and exposing the infection to their families. Web-based psychological interventions that could provide knowledge on managing mental distress and consulting services were highly demanded among HCWs.Conclusion: The prevalence of psychological stress among HCWs in Vietnam during the COVID-19 pandemic was high. There were also significant risk factors associated with it. Psychological interventions involving web-based consulting services are highly recommended to provide mental health support among HCWs.