The issues and problems of mandatory vaccination policy and roll out in First Nations communities are unique and do not concern the safety and effectiveness of vaccines. These issues are also independent of more specific arguments of mandatory vaccination of healthcare workers as a condition of employment. As important as these issues are, they do not consider the complex politics of ongoing settler colonialism and First Nations community relations. In this paper, we also set aside the very real problems of (...) disinformation, hesitancy, scientific and health illiteracy, and other concerns that drive vaccine hesitancy and refusal. These affect all communities, including First Nations communities. We, instead describe the dominant arguments in favour of mandatory vaccination and critique them in terms of the disputed legitimacy of Settler-Colonial decision-making as it impacts First Nations communities. We contend cultural responsiveness and safety—not state compulsion—must remain the first principles of any engagement—including vaccination—with First Nations Peoples, families, and communities. (shrink)