Abstract : Work-related burnout seriously affects all healthcare workers (HCWs). Frontline HCWs, primarily nurses, who treat patients with COVID-19 are more likely to burn out. This study aimed at assessing the factors associated with work-related burnout among nurses during the COVID-19 pandemic. Participants’ demographics, relevant characteristics, stress, anxiety, depression, and COVID-19-related stress items were also assessed and examined for associations with work-related burnout. A cross-sectional, descriptive, correlative design was used to assess factors associated with work-related burnout among nurses during the COVID-19 pandemic. Valid and reliable self-reported questionnaires were used to evaluate COVID-19-related stress items, burnout, stress, anxiety, and depression. A sample of 726 nurses was enrolled in this study. Nurses reported high means of work-related burnout (20.31 ± 6.34). 15.1, 30.9, and 18.3 nurses reported stress, anxiety, and depression, respectively. This study found that work-related burnout was significantly associated with anxiety, stress, and depression (p-value < 0.001). Age, COVID-19-related items, stress, and depression were all significant predictors of burnout among nurses. These four factors could explain 51% of nurses’ burnout during the COVID-19 pandemic. Our study demonstrated high levels of stress, anxiety, depression, and work-related burnout among nurses during the COVID-19 pandemic. Age, stress, depression, and COVID-19 related-stress acted as independent predictors for work-related burnout. To ensure support is available to nurses at risk, existing psychological support interventions must be evaluated using targeted approaches.