Extracorporeal carbon dioxide removal (ECCO₂R) is a low blood flow veno-venous extracorporeal membrane oxygenation technique that provides artificial blood CO₂ removal. Recently, a new ECCO₂R system (PrismaLung), providing very low blood flow has been commercialized. The aim of this study is to report its use in severe chronic obstructive pulmonary disease (COPD) patients needing an ECCO₂R therapy. Six severe COPD patients with acute exacerbation leading to refractory hypercapnic respiratory acidosis were treated with ECCO₂R therapy. Two different systems were used: a PrismaLung system and a conventional ECCO₂R device. The maximum blood flow provided by PrismaLung was significantly lower than that with the conventional ECCO₂R system. In three patients initially treated with PrismaLung, there were no improvements in pH, PaCO₂, or RR. Thus, the therapy was switched to a conventional ECCO₂R system in these three patients, and three others were treated from the outset by the conventional ECCO₂R system, providing significant improvement in pH, PaCO₂, and RR. The present retrospective study describes the first use of PrismaLung in severe COPD patients with acute exacerbation. When compared with a higher blood flow ECCO₂R system, our results show that this novel, very low-flow device is not able to remove sufficient CO₂, normalize pH or decrease respiratory rate.