Objectives: The current study aimed to detect the BOS prevalence and determinants among residents working during the second wave of the COVID-19 pandemic in an Egyptian tertiary university referral hospital. Methods: A crosssectional study evaluating the working period from June to November 2020 during the COVID-19 pandemic second wave, through a five sections questionnaire evaluating: 1 − sociodemographic characteristics, 2 − job characteristics, 3 − negative thoughts related to their job, 4 − resident’s health problems, and 5 − evaluating BOS through Maslach Burnout Inventory (MBI) scale (including emotional exhaustion [EE], depersonalization [DP], and personal accomplishment [PA] as subscales). Results: We included 230 residents with a median age of 27 years. The median MBI sub-scales (IQ Range) values were 30.0 (20, 39), 21.0 (15, 30), and 29.5 (22, 36) for EE, DP, and PA, respectively. About 51.0% and 83.0% of the residents were high in EE and DP, while 8.7% were low in PA. The median EE and DP were higher in younger age (⩽27 years; p=.002 and .024), males (p=.001 and 90 hours weekly (p=.016 and <.001), exposure to harassment (p<.001), and having COVID-19 infection (p=.002 and .001). Residents working in surgical departments reported higher DP scores than those in non-surgical departments (p=.03). There was a mild positive correlation between working hours per week and the total scores in EE and DP, r=.24 (p<.001) and r=.23 (p=.001) respectively, while it was found to have a negative correlation with the PA (r=−.133 and p=.044). Conclusions: The BOS is evident and considerably high among the residents working during the COVID-19 pandemic. Younger age, males, working in surgical departments, and those who got COVID-19 infection were most vulnerable.