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PURPOSE: The current study addressed work-related stress and burnout experienced by health care workers (HCWs) in Cairo University isolation hospital and its impact on the cognitive domain of their executive functioning. METHODS: Arabic validated questionnaires of Beverly Potter for sources of work-related burnout and Maslach Burnout Inventory Human Services Survey for evaluation of burnout degree of 81 HCWs were used. Wisconsin Card Sorting Test was used to examine the HCWs cognitive executive functioning during hospital work and 2 weeks after home isolation. RESULTS: A high degree of work-related stress was evident by a high score on Beverly questionnaire with a mean ± SD of (132.08 ± 12.573). A high degree of burnout was marked with a mean ± SD of (28.48 ± 6.622) for Emotional Exhaustion module, (31.85 ± 5.439) Personal Achievement, and (17.52 ± 6.707) Depersonalization. Health care workers experienced impairment of executive functioning in the form of increased total errors of Wisconsin Card Sorting Test during hospital shifts compared to 2 weeks after. There is a positive significant correlation between work-related stress level and Maslach Burnout Inventory and the total errors of Wisconsin Card Sorting Test results during the hospital stay (p = < 0.001), as well as 2 weeks after (p = < 0.001).This cognitive decline manifested in increased errors during HCWs' clinical work. CONCLUSIONS: Health care workers on the front line experienced a high degree of work-related stress in addition to burnout in the form of Emotional Exhaustion, Depersonalization, and reduced Personal Achievement. They also suffered from impaired cognitive executive functioning due to such stressful exposure.