BackgroundThe COVID-19 epidemic has brought significant changes and complexities to nurses’ working conditions. Given the crucial role of health workers, particularly nurses, in providing healthcare services, it is essential to determine the nurses’ workload, and its association with the quality of work life (QWL) during COVID-19 epidemic, and to explain the factors predicting their QWL.MethodsA total of 250 nurses, who provided care for patients with COVID-19 in Imam Hossein Hospital of Shahrud, and met the inclusion criteria, were considered the samples in the present cross-sectional study in 2021–2022. Data were collected using the demographic questionnaire, NASA Task Load Index (TLX), and Walton’s QWL questionnaire, which were analyzed using SPSS26 and based on descriptive and inferential statistical tests. A p-value less than 0.05 was considered significant for all cases.ResultsThe nurses’ mean scores of workload and QWL were 71.43 ± 14.15 and 88.26 ± 19.5, respectively. Pearson’s correlation test indicated a significant inverse relationship between workload and QWL (r=-0.308, p < 0.001). The subscales with the highest perceived workload scores were physical demand and mental demand (14.82 ± 8.27; 14.36 ± 7.43), respectively, and the subscale with the lowest workload was overall performance (6.63 ± 6.31). The subscales with the highest scores for QWL were safety and health in working conditions and opportunity to use and develop human capabilities (15.46 ± 4.11; 14.52 ± 3.84), respectively. The subscales with the lowest scores were adequate and fair compensation, work and total living space (7.46 ± 2.38; 6.52 ± 2.47), respectively. The number of children (β = 4.61,p= 0.004), work experience (β= -0.54,p= 0.019), effort (β = 0.37,p= 0.033) and total workload (β= -0.44,p= 0.000) explained 13% of the variance of nurses’ QWL.ConclusionsThe study’s findings showed that a higher workload score is associated with nurses’ lower perception of QWL. In order to improve the QWL of nurses, reducing the physical and mental demands of their workload and strengthening overall performance is necessary. Additionally, when promoting QWL, adequate and fair compensation and the work and living space should be considered. The researchers suggest that hospital managers should make more significant efforts to develop and promote the QWL of nurses. To achieve this goal, organizations can pay attention to other influential factors, primarily by increasing organizational support.