In patients with chronic obstructive pulmonary disease (COPD), single lung transplantation (SLT) is sometimes performed as an alternative to bilateral lung transplantation due to limited organ availability. However, the postoperative management of SLT presents challenges, including complications related to the distinct compliance of each lung. This case report presents the case of a 65-year-old male patient who underwent SLT and was in the weaning period from mechanical ventilation. High-flow oxygen therapy (HFOT) was administered, and the physiological effects were measured using electrical impedance tomography (EIT). The results demonstrated that the application of HFOT increased air trapping and overdistention in the native lung without benefiting the transplanted lung. HFOT through a tracheostomy tube or nasal cannula resulted in a more heterogeneous distribution of ventilation, with increased end expiratory lung impedance, prolonged expiratory time constants, and an increase in silent spaces. The drop in tidal impedance after applying HFOT did not indicate hypoventilation but rather overdistention and air trapping in the native lung, while the transplanted lung showed evidence of hypoventilation. These findings suggest that HFOT may not be beneficial for SLT patients and could potentially worsen outcomes. However, due to the limited scope of this case report, further prospective studies with larger patient cohorts are needed to confirm these results.