BACKGROUND: Due to the COVID-19 pandemic in Iran, the number of patients admitted to hospitals and the workload of nurses has increased. High workload can reduce efficiency and quality of life. In the meantime the percived social support may had a moderating role. OBJECTIVE: The aim of the study was to investigate the effect of workload and perceived social support on quality of life in nurses who work in COVID-19 inpatient wards. METHODS: This was a cross-sectional descriptive-analytic study. 336 nurses who worked in inpatient wards with COVID-19 patients were randomly selected and studied. NASA-TLX Workload Questionnaire, WHO Quality of Life Questionnaire and Multidimensional Social Support Perception Scale were used to data collection. Structural equation modelling in PLS software was used to modelling. RESULTS: The results showed that the average score of workload, perceived social support and quality of life were 80.87±20.17, 56.23±11.46 and 55.87±13.74, respectively. A significant inverse relationship was observed between workload and quality of life (P <  0.05). Also, perceived social support had a moderator effect on relationship between workload and quality of life (P <  0.05). CONCLUSIONS: High workload can upset the balance between work and life that leads to decrease the quality of life. Perceived social support as a moderator can reduce the negative impact of workload on quality of life. In the COVID-19 pandemic where nurses’ workload have increased, by increasing the perceived social support can manage the negative effect of workload.