Introduction: This study investigated differences between rural Australian First Nations and non-First Nations survey respondents’ perceptions of COVID-19-related risks and analysed other variables that could predict an exacerbation of anxiety related to COVID-19 harms. Methods: A cross-sectional online and paper survey of rural residents from the western regions of NSW, Australia, was conducted. Descriptive and multivariate statistical analyses were used to assess links between First Nations status and demographic measures including postcode, age, gender, education, rural or town/village location, proximity to medical services and living situation. The analysis included five items related to perceptions about COVID-19: perceived likelihood of contracting COVID-19 in the next 12 months, perceived harmfulness of the virus, how often people felt afraid, perception about respondents’ ability to do something about the virus and perceived economic impacts of the pandemic. Results: There were significant differences between First Nations (n=60) and non-First Nations (n= 639) respondents across all sociodemographic categories. The results reflect a significantly higher level of anxiety among the First Nations Australians in the sample: they felt afraid more often, felt it was highly likely they would catch the virus and if they did catch the virus perceived that it would be very harmful. Living with children under eighteen years of age and in small rural towns were key factors linked to feeling afraid of COVID-19 and First Nations status. Conclusion: Health risk communication in pandemic response should include an equitable focus on rural areas, recognising that First Nations Australians are a significant proportion of the rural population with different risk factors and concerns than those of non-First Nations Australians. This principle of First Nations-led design is critical to all health policy and planning. The Australian Government should include rural areas in planning pandemic responses, recognising that First Nations populations are a significant proportion of the rural population creating syndemic conditions.