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.