Abstract Substance use is associated with increased risk of, progression to, and negative outcomes from chronic disease. Although associations between substance use and chronic disease are well documented, specific mechanisms underlying these associations are poorly understood and underappreciated. There is a pressing need for innovative, prospectively-designed, longitudinal studies that can clarify how biopsychosocial variables contribute to linkages between substance use and chronic disease. However, coordinating and obtaining the scientific expertise, clinical acumen, equipment, and other resources needed for these studies can be difficult and time consuming, particularly for early-career scientists. Providing these resources through a research core can enhance investigator productivity and promote scientific rigor and reproducibility. Thus, the overall aim of the CADRE’s Clinical Laboratory Core (CLC) is to support research led by CADRE investigators, other investigators at Brown University, and investigators from other IDeA-state institutions who are conducting research on substance use and chronic disease, by identifying and providing the scientific expertise, clinical acumen, technical capability, and other resources necessary to meet the needs of their projects. These resources build on and complement, but do not overlap, resources currently available at Brown. Specific Aim 1 of the CLC is to provide the resources necessary for conducting both in-person and remote human subjects research on substance use and chronic disease. Specific Aim 2 is to create a business plan that expands the user base of the CLC, utilizes a fee-for-service model of cost recovery, and enables the CLC to be self- sustaining when COBRE funding ends. Specific Aim 3, an exploratory aim, is to continue to build a center-wide database of transdiagnostic risk factors associated with the development and progression of SUDs and chronic disease. The successful achievement of these aims will be a thematically- and technically-linked center that supports the initial and future projects, enhances the competitiveness of the project leaders for independent external funding, becomes a national leader in understanding biobehavioral mechanisms linking SUDs and chronic disease, and serves as a resource for training and research within Brown, regionally, and nationally.