ABSTRACT More than 63% of US adults are employed, and work exerts an independent, powerful influence on their health. At UNC Chapel Hill, our recognition of the role of work in health has driven our long history of occupational safety and health promotion activities, including surveillance, basic etiology, intervention and translation research, practice, and influence on public policy. As we conducted needs and strengths assessments in preparation for this Center proposal, we saw how the COVID-19 pandemic created a massive re-shaping of work, work conditions, and worker health – particularly related to mental health and well-being among essential workers. This observation created tremendous interest among investigators at UNC Chapel Hill, the NC Occupational Safety and Health Education Research Center, UNC's Center for Health Promotion and Disease Prevention and Injury Prevention Research Center, collaborators at Duke University and UNC Greensboro, and key stakeholders from public and private sectors to join forces to establish a new Carolina Center for Total Worker Health and Well-Being. The mission of the Carolina Center is to generate new knowledge and implement activities to improve worker health and well-being in North Carolina, the southeast region, and the nation. Strong leadership, national experts on our External Advisory Committee (EAC) and at RTI International will work with us to conduct the overall Center evaluation, with a goal of continuous quality improvement that informs strategic planning efforts. Within the Center's Pilot Project Program, we will employ data-driven approaches to prioritize proposals funded, be responsive to emerging issues, and support the work of the four proposed research projects which address three essential worker groups (nurses/physicians, firefighters and childcare) and an under-studied group of LGBTQ workers. Given the current and growing needs we identified, we will focus our attention on mental health and well-being of these workers, as well as traditional occupational safety outcomes such as slips, trips and falls. We will investigate different participatory approaches to engaging with workers and other stakeholders as we move the research enterprise from basic etiology and surveillance, to intervention and translation. Our Center's work directly addresses NORA and TWH Research Agenda priorities with important, innovative research, as well as outreach and education activities that will communicate the benefits of a TWH approach to businesses and key stakeholders, translate our findings and disseminate them to improve policy and practice, and build capacity for TWH among new and current occupational safety and health professionals through the expansion of our existing TWH certificate to non-degree seeking health professionals. As evidenced by enthusiastic letters of support from existing partners at UNC, our EAC members and others in Region 4, and several other TWH Center representatives, the Carolina...