The coronavirus disease 2019 (COVID-19) pandemic has put considerable physical and emotional strain on frontline healthcare workers. Among frontline healthcare workers, physician trainees represent a unique group-functioning simultaneously as both learners and caregivers and experiencing considerable challenges during the pandemic. However, we have a limited understanding regarding the emotional effects and vulnerability experienced by trainees during the pandemic. We investigated the effects of trainee exposure to patients being tested for COVID-19 on their depression, anxiety, stress, burnout and professional fulfillment. All physician trainees at an academic medical center (n = 1375) were invited to participate in an online survey. We compared the measures of depression, anxiety, stress, burnout and professional fulfillment among trainees who were exposed to patients being tested for COVID-19 and those that were not, using univariable and multivariable models. We also evaluated perceived life stressors such as childcare, home schooling, personal finances and work-family balance among both groups. 393 trainees completed the survey (29% response rate). Compared to the non-exposed group, the exposed group had a higher prevalence of stress (29.4% vs. 18.9%), and burnout (46.3% vs. 33.7%). The exposed group also experienced moderate to extremely high perceived stress regarding childcare and had a lower work-family balance. Multivariable models indicated that trainees who were exposed to COVID-19 patients reported significantly higher stress (10.96 [95% CI, 9.65 to 12.46] vs 8.44 [95% CI, 7.3 to 9.76]; P = 0.043) and were more likely to be burned out (1.31 [95% CI, 1.21 to1.41] vs 1.07 [95% CI, 0.96 to 1.19]; P = 0.002]. We also found that female trainees were more likely to be stressed (P = 0.043); while unmarried trainees were more likely to be depressed (P = 0.009), and marginally more likely to have anxiety (P = 0.051). To address these challenges, wellness programs should focus on sustaining current programs, develop new and targeted mental health resources that are widely accessible and devise strategies for creating awareness regarding these resources.