Background: Physicians during the COVID-19 pandemic are working under relentless stress. This study aimed to identify the impact of the perceived fears of COVID-19 virus infection on the quality of life and the emergence of burnout syndrome among physicians in Egypt during the COVID-19 outbreak. This cross-sectional study was conducted between May 10th and June 9th, 2020, and included 320 Egyptian physicians who were working during the outbreak of the COVID-19 pandemic. The participants were interviewed using the Fear of COVID-19 scale (FCV19S), Hospital Anxiety and Depression Scale (HADS), Maslach Burnout Inventory, and World Health Organization Quality of Life Scale (WHOQOL-BREF) for assessment of the perceived fears of COVID-19 virus infection, associated anxiety and depressive symptoms, burnout symptoms, and quality of life, respectively. Results: Overall, most physicians were females (63%). Ideas about death, moderate-to-severe anxiety, and depressive symptoms were reported by 11, 28, and 29% of physicians, respectively. For burnout symptoms, high emotional exhaustion, high depersonalization, and low personal accomplishment were reported by 20, 71, and 39% of physicians, respectively. The perceived fear of COVID-19 virus infection was positively correlated with anxiety, depression, and burnout emotional exhaustion, and depersonalization symptoms, and negatively correlated with personal accomplishment and all quality of life domains. Conclusions: Egyptian physicians experienced higher levels of COVID-19-related fears, anxiety, and depressive and burnout symptoms. There was a robust correlation between these perceived fears, and higher burnout symptoms, and poor quality of life among physicians. Specific interventions should be tailored to minimize the physical and mental burdens on the physicians during the COVID-19 pandemic.