A previously healthy 7-month-old male infant presented for evaluation of fever, deceased oral intake, and intermittent noisy breathing. Physical examination revealed neck tenderness. Soft tissue neck radiographs and computed tomography (CT) scan supported a diagnosis of retropharyngeal swelling with extension to the superior mediastinum. Surgical exploration was planned, and endotracheal intubation was performed in the operating room. Significant cardiorespiratory derangements developed immediately after the tracheal tube was inserted, including hypotension, hypoxia, and bradycardia with signs of cardiac ischemia. The patient was resuscitated with intravenous fluids, vasopressors, and bronchodilators; his condition improved after resuscitation and surgical evacuation of purulent material. A combination of mediastinal mass effect, aspiration, and bronchospasm likely contributed to the patient’s deterioration. The subsequent clinical course was uneventful. The patient was extubated in a delayed fashion and discharged on the fourth postoperative day. This case highlights the importance of preparing for a difficult airway in cases of retropharyngeal abscesses that necessitate tracheal intubation. A multidisciplinary approach is best suited to manage the airway, preferably in the operating room.