Background: COVID-19 pandemic has not only caused an unprecedented distress in the community, but also significant physical and psychological exhaustion amongst healthcare workers (HCWs), that could lead to serious effects on our healthcare system. This study was conducted to assess burnout among oncologists and other healthcare professionals at a large academic center. Methods: An electronic 10-minute questionnaire was sent to actively employed physicians, APRNs and PAs at the University of Miami. Survey items evaluated various personal and professional characteristics including COVID related stress. Burnout was examined with Maslach Burnout Inventory (MBI), which evaluated severity across two domains: emotional exhaustion and depersonalization. The logistic regression model was used to estimate association between study variables and high burnout levels. Odds ratio (ORs) and corresponding 95% confidence interval (CI) were obtained. Continuous variables were tested using two-sample t-test by high burnout status. Results: The survey was sent to 739 HCWs, out of which 182 (24.6%) completed the entire survey; 63.7% were physicians, 8.6% fellows, and 27.4% APRN or PA. The pandemic led to rescheduling of professional activities (22.2%), increased workload (59.5%), job insecurity (28.6%), and decreased leadership opportunities (32.2%). 62.3% of respondents reported decreased exercise; 44.8% reported new sleep disorder; 56.1% reported increased home responsibilities; childcare arrangements were affected in 60.6%; 61.4% struggled to maintain work-life balance. 70 of 182 respondents were broadly from the fields of Oncology and Palliative Care. 9 out of these 70 respondents reported high depersonalization, 27 reported high emotional exhaustion, and 33 reported overall high burnout symptoms on either emotional exhaustion or depersonalization scales. Amongst physicians holding positions from PGY4 through licensed attendings with less than 5 years’ experience, 62.5% (95%CI=35.4-84.8) showed high burnout rate (10 of 16), which was not statistically different from older physicians (11 of 27=40.7% (95%CI=22.4-61.2)). No difference in burnout was seen for other study variables including gender, marital status, and race/ethnicity. Conclusions: COVID-19 pandemic has incited not only an unmatched level of practice changes, but also extraordinary psycho-social uncertainty, leading to a considerable impact on HCWs’ wellbeing. Long working hours, lack of sleep, fear of losing job, transition to tele-medicine, risk of getting infection and putting their family at risk, lack of childcare, pressure of home schooling- all seem to have caused an increased physical and psychological pressure among HCWs and warrants an examination of potential coping mechanisms. This study sets the stage for more elaborate research to illustrate and guide the development of wellness programs imperative to the well-being of HCWs.