Aim: The aim of this study was to assess the influence of perceived work environment, empowerment and psychological stress on job burnout among nurses working at the time of the COVID-19 pandemic. Background: Nurses experienced high levels of job burnout during the pandemic, which impacted their mental health and well-being. Studies investigating the influence of work environment, empowerment and stress on burnout during the time of COVID-19 are limited. Design: The study utilized a cross-sectional design. Methods: Data were collected from 351 nurses in Oman between January and March 2021. The Maslach Burnout Inventory, the Practice Environment Scale of the Nursing Work Index, the Conditions of Work Effectiveness Questionnaire and the Perceived Stress Scale were used to assess study variables. Results: About two-thirds of the nurses (65.6%) reported high levels of job burnout. Nurse managers' ability, leadership and support; staffing and resources adequacy; and nurses' access to support were significant factors associated with a reduced level of burnout. Conclusion: Supporting nurses during the crisis, ensuring adequate staffing levels and providing sufficient resources are critical to lower job burnout. Creating a positive and empowered work environment is vital to enhance nurses' retention during the pandemic.