Abstract In the Oil Sands Regions of Alberta, Canada, Indigenous reassertion of rights and responsibilities has lead to a renewed leadership in monitoring the effects of industries on various environment receptors. This study, conducted with Cold Lake First Nations, Alberta (CLFN), sought to explore local concerns regarding fish consumption safety and population health in response to multiple anthropogenic stressors focusing upon oil extraction. We undertook this work using a novel research design comprised of two distinct approaches including a participatory fish health and toxicology study and a cultural consensus survey of CLFN members. The cultural consensus study assessed similarities and differences in knowledge and perceptions of CLFN members. The fish toxicology and health research involved implementing a co-designed protocol to collect and sample fish for toxicants and overall population health using scientific indicators. We discuss the results of each study as well as the tangible application of our work in achieving a Multiple Evidence Base approach. Our work highlights that complementarities between our studies as part of a negotiated research process can form a single cohesive narrative to better inform fisheries management while respecting community knowledge, culture and rights to access land, water and country foods.