Healthcare workers worldwide have been exposed to extraordinary stress during COVID-19 pandemic. This study aimed to investigate health-related quality of life (HRQoL) level and its health and occupational associated factors among Jordanian physicians during COVID-19 pandemic. A cross-sectional design using an online survey was adopted targeting physicians at different Jordanian hospitals. The study survey included demographics, HRQoL measured by 12-item Short Form health survey (SF-12) mental and physical components, physicians’ evaluation of work conditions during COVID-19, Neck Disability Index (NDI), Depression Anxiety Stress Scale (DASS 21), and International Physical Activity Questionnaire (IPAQ). Descriptive analyses were conducted to summarize primary data. Factors associated with HRQoL were determined using a multiple variable regression analysis. In total, 326 physicians successfully completed the survey, 44.2% were males with mean age of 32.08 (±6.93). SF-12 mental component mean was 52.13 (±20.84) and physical component mean was 69.24 (±18.1). Physicians HRQoL level was significantly associated with levels of stress (β = −0.23, 95% CI −1.05 to −0.27), depression (β = −0.22, 95% CI −1.09 to −0.28), neck disability (β = −0.30, 95% CI −1.08 to −0.57), health self-evaluation (β = 0.14, 95% CI 1.66–7.87), sleep self-evaluation (β = 0.09, 95% CI 0.16–3.58), and physical activity level (β = 0.09, 95% CI 0.00–0.001). Jordanian physicians’ level of HRQoL was relatively low during COVID-19. Healthcare facilities administrators should take into consideration factors associated with physicians’ HRQoL level when planning for future healthcare emergencies.