BACKGROUND: Livestock disease outbreaks are challenging to control and often lead to animal deaths, sometimes necessitating the mass euthanasia of an entire herd or flock, a process known as depopulation. Depopulation is essential for safeguarding animal welfare, human health, and economic stability, as well as preventing the further spread of disease. While significant advancements have been made in the surveillance, detection, and disposal of affected farm animals, less attention has been given to the impact of livestock diseases and depopulation on farmers' mental health. This study explored the mental health effects of these events on farmers and identified strategies to enhance their resilience in coping with such stress. METHODS: Using a qualitative study, 20 farmers, veterinarians, and industry experts were recruited to describe the experience of livestock diseases and depopulation in Alberta, Canada through semi-structured, one-on-one interviews. All had experience with livestock diseases, and 18 had direct depopulation experience. To capture a broad spectrum of the impact on farmers, we gathered feedback from those raising cattle, swine, poultry, deer and elk, sheep, goats, and bees. The interviews were analyzed using a thematic approach to identify common themes. RESULTS: Five themes and five sub-themes emerged from the analysis: emotional distress (with sub-themes of shock and helplessness, anxiety and hypervigilance, despondency and waning motivation, fear of judgment and stigma, and contextual variables), threats to identity, economic burden, distrust and frustration with authorities, resilience and adaptation. Using our findings, we adapted the Emergency Management Framework to show what activities could be integrated to support farmers' mental health needs before, during, and after a depopulation event. CONCLUSION: Farm animal diseases threaten the livelihoods and well-being of farmers as well as pose a significant threat to Canada's food security and national economy. Our findings indicate farmers who experience livestock diseases and depopulation may be at risk for poor mental health. Implications for education and training, as well as changes to policy to support the mental health and well-being of farmers is discussed.