Background: Burnout is common among physicians and physician leaders, including residency program directors (PDs). The effects of the COVID-19 pandemic and other stressors in 2020 on PDs is unknown. Objective: To measure the prevalence of burnout among internal medicine (IM) residency PDs 6 months into the COVID-19 pandemic. Methods: A total of 429 IM PDs, representing 83% of accredited residency programs, were surveyed from August to December 2020. Burnout, using a 2-item screening tool, and self-reported consideration of resigning in 2020, were compared to their annual prevalence since 2012 and tested for possible associations with pandemic stressors and program characteristics. Results: The survey response rate was 61.5% (264 of 429). One-third (33.6%, 87 of 259) of PD respondents met burnout criteria, and 45.1% (110 of 244) reported considering resigning in the past year, which were within the range of preceding years. PDs who reported feeling highly supported by institutional leadership were less likely to meet burnout criteria and to have considered resigning. There were no associations between burnout or consideration of resigning and the amount of clinical time PDs spent in their roles, duration of maximum stress on programs, budget cuts to programs, or geographic region. Conclusions: The prevalence of burnout among PDs in fall 2020 was similar to the prevalence of burnout in pre-pandemic years despite uniquely extreme stressors. PDs' perception of being highly supported by institutional leadership was associated with lower prevalence of burnout and consideration of resigning. Perceived leadership support may be a protective factor against burnout during periods of high stress.