Emerging research increasingly links climate change to infectious disease outcomes, including zoonotic transmission and spillover events and destruction of health-supporting infrastructure (ie, housing, nutrition, sanitation, and healthcare). However, Indigenous communities have understood the interdependence of ecological and human health for millennia. This knowledge is encompassed by relationality, an ontological and epistemological stance that revolves around relationships with relatives (including landscapes, animals, plants, humans, ancestors, and spiritual entities). Relational methodologies prioritize interdisciplinary thinking and reciprocity between learners, subjects of interest, and community. Without exploiting or appropriating knowledge from any specific Indigenous community, we illustrate a generalized concept of relationality that is applicable to infectious disease research. Relational methods reveal historic and ongoing colonialism as fundamental causes of both climate change and infectious disease. These issues will never be fully understood without accounting for colonialism and its entanglements with pathogens and the science that studies them. Climate and health research will be improved through application of relational methods and active repair of ongoing colonial violence.