Background First Nations (FN) people of Canada experience health, social, and systemic inequities due to colonization. Consequently, COVID-19 has placed further mental health stress on people related to personal finances, employment security and worry over infection, resulting in exacerbated effects of unresolved past medical and physical traumas. This study aims to understand the experiences related to mental health in an Alberta FN community during the early stages of the pandemic. Methods In partnership with FN leadership, the study implemented an online cross-sectional survey. Adults from a large FN community in Alberta, Canada, were asked to complete a survey, including two mental health-related screening questionnaires: (1) Generalized Anxiety Disorder-2 item; and (2) Patient Health Questionnaire-2 item. In addition, respondents could provide responses to open-ended questions about their experiences. Results Among 106 respondents, 95 (89.6%) finished the survey; 18% of adults screened positive for depressive symptoms (score of 3 or greater) and reported difficulty following public health advice for using hand sanitizer, maintaining social distancing, or self-isolating. 21% of adults screened positive for symptoms of anxiety (score of 3 or greater) and reported difficulty maintaining social distance, self-isolating, obtaining food and clothing, or meeting other basic living requirements. Conclusions FN communities may be disproportionately affected by COVID-19, and may experience exacerbated symptoms of anxiety, depression and overall poor mental health and well-being. Additional supports and services, including for mental health, should be considered for FN in the context of COVID-19 public health measures.