A 16-month-old castrated male Great Dane was presented to Cornell University’s Hospital for Animals on referral for respiratory difficulty, lethargy, inappetence, and weight loss. Thoracocentesis was performed and microscopic analysis revealed septic suppurative pleural fluid. Bilateral large-bore chest tubes were placed on continuous suction and thoracic ultrasound and computed tomography (CT) scan were consistent with right-sided pneumo-hydrothorax, lung consolidation, and thickened pleura. After unsuccessful medical management, lung bilobectomy was performed under general anesthesia using one lung ventilation technique. The patient was discharged within a few days postoperatively and made a full recovery.