In Canada, colonisation, both historic and ongoing, increases Indigenous vaccine hesitancy and the threat posed by infectious diseases. This research investigated Indigenous vaccine hesitancy in a First Nation community in Saskatchewan, ways it can be overcome, and the influence of a colonial history as well as modernity. Research followed Indigenous research methodologies, a community-based participatory research design, and used mixed methods. Social media posts (interventions) were piloted on a community Facebook page in January and February (2022). These interventions tested different messaging techniques in a search for effective strategies. The analysis that followed compared the number of likes and views of the different techniques to each other, a control post, and community-developed posts implemented by the community’s pandemic response team. At the end of the research, a sharing circle occurred and was followed by culturally appropriate data analysis (Nanâtawihowin Âcimowina Kika-Môsahkinikêhk Papiskîci-Itascikêwin Astâcikowina procedure). Results demonstrated the importance of exploring an Indigenous community’s self-determined solution, at the very least, alongside the exploration of external solutions. Further, some sources of vaccine hesitancy, such as cultural barriers, can also be used to promote vaccine confidence. When attempting to overcome barriers, empathy is crucial as vaccine fears exist, and antivaccine groups are prepared to take advantage of empathetic failures. Additionally, the wider community has a powerful influence on vaccine confidence. Messaging, therefore, should avoid polarising vaccine-confident and vaccine-hesitant people to the point where the benefits of community influence are limited. Finally, you need to understand people and their beliefs to understand how to overcome hesitancy. To gain this understanding, there is no substitute for listening.