BACKGROUND: Occupational burnout in a pandemic situation occurs faster for some people than others. This study aimed to evaluate the relationship between personality traits and occupational burnout in nursing professionals during the COVID-19 pandemic. MATERIALS AND METHODS: An observational, cross-sectional study was conducted from February to April 2021. This was carried out on 299 nursing professionals who were taking care of COVID-19 cases. Occupational burnout was measured by the Maslach Burnout Inventory, and personality variables were evaluated using the NEO fivefactor inventory. RESULTS: Finally, 299 nurses with a mean age of 35.49 ± 8.80 years participated in the study, of which 74.9% were women and 77.3% were married. The mean scores of emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA) subscales were 20.44 ± 11.52, 8.75 ± 4.10, and 27.66 ± 5.92, respectively. High and medium DP and EE levels were reported in 75.2% and 54.9% of the nurses and high PA level was found in 87.6%. There were significant differences in job satisfaction and work experience for all burnout subscales scores. DP and EE subscales had a positive relationship with neuroticism and a negative correlation with extraversion, openness, agreeableness, and conscientiousness. The PA subscale showed a statistically significant positive relationship with extraversion, openness, agreeableness, and conscientiousness. CONCLUSIONS: The prevalence of burnout among nurses during the COVID-19 pandemic was moderate to high. The five personality characteristics were significantly associated with burnout in nurses and have a key role in developing burnout syndrome.