A relatively common problem that may arise during one-lung ventilation is elevation of end-tidal carbon dioxide (ETCO2), which has several potential etiologies. This case report describes a 69-year-old woman with carcinoid tumor undergoing a robotic left lower lobectomy complicated by an acute rise in ETCO2 during one-lung ventilation, without an immediately identifiable cause. Thorough evaluation revealed CO2 leak through an open bronchial lumen resulting in an artificially high ETCO2 reading. This case report demonstrates the importance of performing a comprehensive assessment during acute changes in ETCO2 while also considering changes in the surgical field, which may contribute to these findings.