Clostridium-associated necrotizing hepatitis with multiple organ lesions is a rare and severe condition in dogs. Clostridium species, anaerobic bacteria commonly found in the environment, can lead to various infectious diseases in animals. Among these, Clostridium novyi type B has been identified as a causative agent of necrotizing hepatitis. This case study presents a 4.5-year-old spayed female Golden Retriever with acute-onset lethargy, decreased appetite, and vomiting. Post-mortem examination revealed liver lesions consistent with Clostridium-associated necrotizing hepatitis and significant pathology in the kidneys, heart, and spleen, indicating multi-organ involvement. Histopathological examination further supported the diagnosis, highlighting panlobular hepatocytic necrosis, endospore forming bacilli, and toxin-related damage. While the pathophysiology underlying this condition remains incompletely understood, it is hypothesized that bacterial endospores reach the liver via the portal circulation, where they germinate and release toxins. The toxins impact endothelial cells, hepatocytes and other organs causing cellular detachment, necrosis and fluid leakage. Furthermore, systemic dissemination of bacteria may play a crucial role in this process. Bacterial endospores might disseminate through the bloodstream, reaching distant organs, including the kidneys, lungs, heart, and spleen, leading to multi-organ involvement. This case underscores the rarity and complexity of Clostridium-associated necrotizing hepatitis in dogs, especially with multi-organ involvement, and highlights the need for comprehensive understanding and further research in this area.