Resident physicians face a higher rate of burnout and depression than the general population. Few studies have examined burnout and depression in Canadian laboratory medicine residents, and none during the COVID-19 pandemic. To identify the prevalence of burnout and depression, contributing factors, and the impact of COVID-19 in this population. An electronic survey was distributed to Canadian laboratory medicine residents. Burnout was assessed using the Oldenburg Burnout Inventory. Depression was assessed using the Patient Health Questionnaire 9. Seventy-nine responses were collected. The prevalence of burnout was 63% (50 of 79). The prevalence of depression was 47% (37 of 79). Modifiable factors significantly associated with burnout included career dissatisfaction, below average academic performance, lack of time off for illness, stress related to finances, lack of a peer or staff physician mentor, and a high level of fatigue. Modifiable factors significantly associated with depression further included a lack of access to wellness resources, lack of time off for leisure, and fewer hours of sleep. Fifty-five percent (41 of 74) of participants reported direct impacts to their personal circumstances by the COVID-19 pandemic. Burnout and depression are significant issues affecting Canadian laboratory medicine residents. As the COVID-19 pandemic continues, we recommend the institution of flexible work arrangements, protected time off for illness and leisure, ongoing evaluation of career satisfaction, formal and informal wellness programming with trainee input, formal mentorship programming, and a financial literacy curriculum as measures to improve trainee wellness.