Carbon monoxide (CO) poisoning is a leading cause of toxic exposure-related morbidity and mortality worldwide. Although hyperbaric oxygen therapy increases CO elimination, its clinical use is limited by accessibility, side effects, and inconclusive long-term efficacy. We developed a cEHT system – a device for continuous extracorporeal hyperoxygenation therapy that enhances CO removal from blood without exposing patients to systemic hyperbaric conditions. The system was tested in vitro and in vivo in a porcine CO poisoning model. Carboxyhemoglobin (COHb) half-life, hemodynamics, hemolysis, and tissue hypoxia were evaluated. In vivo, the cEHT system significantly reduced COHb half-life by 53% compared to ventilation with 100% oxygen alone (27.0 ± 0.3 min vs. 57.6 ± 12.5 min; p = 0.01). Hemodynamic parameters, pulmonary artery pressure, and plasma-free Hb remained stable during treatment. Histological analyses showed reduced ischemic injury in heart and brain tissues in the cEHT group in contrast to the control group. The cEHT system enables effective and hemodynamically stable extracorporeal CO elimination. It may offer a promising therapy for CO poisoning when a pressure chamber is not promptly available. Further studies are needed to optimize system performance and assess clinical translation.