Objective: To describe the stress prevalence and associated factors among clinical nurses at Saint Paul General Hospital in Hanoi during the COVID-19 epidemic in 2022. Methods: This study applied a cross-sectional study design and was a baseline of an original randomized controlled trial. Data of 400 Saint Paul General Hospital nurses were collected from March 2022 to April 2022 in Hanoi. Self-reported questionnaires included the stress component of the 21-item Depression, Anxiety and Stress Scale (DASS-21) and several demographic and work-related variables. Bivariate and multivariate logistic regression was performed to identify factors associated with nurses’ stress using SPSS 20.0. Results: The prevalence of stress in Saint Paul General Hospital nursing staff was 11.8%. The mean stress score was 7.8 (SD=6.3). Multivariate logistic analysis showed that anxiety and depression were significantly associated with the increased risk of stress among nurses (OR=6.6, 95% CI = 2.3-19.1 and OR=12.5, 95% CI = 5.3-29.5, respectively). Conclusion: Stress was observed among nurses. Its association with anxiety and depression calling for hospital management to consider mental health interventions such as stress management for all nurses to improve their well-beings and quality of services.