Background <p>Swyer-James-Macleod Syndrome (SJMS) is a rare respiratory disease usually caused by obliterative bronchiolitis since childhood and characterized by expiratory air trapping, hypoxia-induced parenchymal destruction, pulmonary hypoperfusion, and impaired gas exchange. Anesthetic management for bronchoscopy in patients with SJMS is challenging due to compromised cardiopulmonary function and shared airway paradigm during the procedure. Herein, we report the use of dexmedetomidine-esketamine combination during anesthesia induction and maintenance for bronchoscopy in a patient with severe SJMS.</p> Case presentation <p>A 39-year-old man with Swyer-James-Macleod Syndrome and severely compromised cardiopulmonary function was scheduled for endoscopic lung volume reduction under a standby extracorporeal membrane oxygenation support. To maintain hemodynamic stability and facilitate withdrawing from mechanical ventilation, we explored the use of dexmedetomidine-esketamine combination as a supplement during induction and maintenance of general anesthesia in this specific critically ill patient. Upon procedure completion, the patient was extubated in the operating room and transferred to the respiratory intensive care unit. Extracorporeal membrane oxygenation support was not required.</p> Conclusions <p>We found that supplemental use of the dexmedetomidine-esketamine combination during general anesthesia for bronchoscopy helped maintain a stable hemodynamic state and facilitate early extubation in this patient with severe SJMS. Our findings provided initial evidence for future clinical investigations.</p>