Case summary A 12-year-old spayed female domestic shorthair cat presented for chest wall resection and radiation therapy following incomplete surgical excision of a feline injection site sarcoma. A CT scan for surgical planning was performed under general anesthesia and showed extensive tumor infiltration of the soft tissues of the right thorax. The cat recovered uneventfully from this anesthetic event. Nineteen days later, the patient was reanesthetized for forequarter amputation plus radical chest wall resection, including ribs 3–8 and all associated soft tissues plus adjacent spinous processes. Postoperatively, the patient developed acute respiratory failure secondary to hypoventilation. The cat was mechanically ventilated for 12 h prior to being successfully weaned from the ventilator. However, the improvement was transient and mechanical ventilation was reinitiated 6 h later owing to respiratory fatigue. On the second day, the cat developed unexplained central nervous system signs and was euthanized. Relevance and novel information To our knowledge, this is the first case report to describe ventilatory failure secondary to radical chest wall resection in a cat. Hypoventilation with subsequent need for mechanical ventilation is a potential complication that should be considered during preoperative planning in patients requiring extensive chest wall resections.