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The current study examined relations among early childhood (ECE) and early childhood special education (ECSE) teachers’ job demands and resources, perceived stress, job burnout, and depressive symptoms using a mediation model. Participants were 143 ECE teachers from private, state-funded, Early Head Start, Head Start programs, and 121 ECSE teachers from inclusive co-teaching classrooms and ECSE classrooms in a northwestern state in the U.S. Teachers completed an online survey. Results indicate that there are some similarities and some differences between these teachers in the links between their job demands and resources, perceived stress, job burnout, and depressive symptoms. Findings will provide a better understanding of ECE and ECSE teachers’ psychological and professional well-being and have implications for their professional development programs.