Objective To explore the moderating effects of sociodemographic and work-related variables on levels of burnout and mental health among medical residents. Method A cross-sectional online survey was administered at the beginning of the second wave of COVID-19 at different public teaching hospitals where medical residents practiced in Mexico City. A total of 201 medical residents of different years completed the survey. Results Different univariate inferential analyses on the level of burnout and mental health indices showed significant differences between sex, marital status, previous reports of physical illness or psychological conditions, and residency ranking. However, the effect sizes of those differences were of low to medium size. A predictive path analysis revealed that the three stages of burnout (emotional exhaustion, depersonalization, and achievement dissatisfaction) negatively affect psychological wellbeing and positively affect psychological distress. Finally, even though sociodemographic variables showed some significant variation, the effect sizes were small and did not moderate the direct effect of burnout on mental health indices. Conclusions Medical residents deling with every day medical situations, will be exposed to stressors that might increase the probability to experience emotional exhaustion. This would negatively affect levels of wellbeing and positively affect distress, despite their sociodemographic characteristics.