Background: Health systems face challenges in using research evidence to improve policy and practice. These challenges are particularly evident in small and poorly resourced health systems, which are often in locations (in Canada and globally) with poorer health status. Although organizational resources have been acknowledged as important in understanding research use resource theories have not been a focus of knowledge translation (KT) research. What resources, broadly defined, are required for KT and how does their presence or absence influence research use?In this paper, we consider conservation of resources (COR) theory as a theoretical basis for understanding the capacity to use research evidence in health systems. Three components of COR theory are examined in the context of KT. First, resources are required for research uptake. Second, threat of resource loss fosters resistance to research use. Third, resources can be optimized, even in resource-challenged environments, to build capacity for KT.Methods: A scan of the KT literature examined organizational resources needed for research use. A multiple case study approach examined the three components of COR theory outlined above. The multiple case study consisted of a document review and key informant interviews with research team members, including government decision-makers and health practitioners through a retrospective analysis of four previously conducted applied health research studies in a resource-challenged region.Results: The literature scan identified organizational resources that influence research use. The multiple case study supported these findings, contributed to the development of a taxonomy of organizational resources, and revealed how fears concerning resource loss can affect research use. Some resources were found to compensate for other resource deficits. Resource needs differed at various stages in the research use process.Conclusions: COR theory contributes to understanding the role of resources in research use, resistance to research use, and potential strategies to enhance research use. Resources (and a lack of them) may account for the observed disparities in research uptake across health systems. This paper offers a theoretical foundation to guide further examination of the COR-KT ideas and necessary supports for research use in resource-challenged environments.