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Burnout symptoms are common among health professionals. Gaps remain in understanding both the stability of burnout and compassion over time and relationships among burnout, self-compassion, stress, and mindfulness in pediatric residents.The authors conducted a prospective cohort study of residents at 31 U.S. residency programs affiliated with the Pediatric Resident Burnout–Resilience Study Consortium. Residents completed online cross-sectional surveys in spring 2016 and 2017. The authors assessed demographic characteristics and standardized measures of mindfulness, self-compassion, stress, burnout, and confidence in providing compassionate care.Of 1,108 eligible residents, 872 (79%) completed both surveys. Of these, 72% were women. The prevalence of burnout was 58% and the level of mindfulness was 2.8 in both years; levels of stress (16.4 and 16.2) and self-compassion (37.2 and 37.6) were also nearly identical in both years. After controlling for baseline burnout levels in linear mixed-model regression analyses, mindfulness in 2016 was protective for levels of stress and confidence in providing compassionate care in 2017. Self-compassion in 2016 was protective for burnout, stress, and confidence in providing compassionate care in 2017; a one-standard-deviation increase in self-compassion score was associated with a decrease in the probability of burnout from 58% to 48%.Burnout and stress were prevalent and stable over at least 12 months among pediatric residents. Mindfulness and self-compassion were longitudinally associated with lower stress and greater confidence in providing compassionate care. Future studies are needed to evaluate the effectiveness of training that promotes mindfulness and self-compassion in pediatric residents.