It is well known that, even at ppm levels, the presence of CO in a PEFC anode feed stream has a significant impact on the MEA performance. Numerous work on short-term CO impact on PEFC performance under steady-state current demands has been carried out. However, to the best of our knowledge, the impact of long-term (i.e., >600 h) CO contamination on intrinsic Pt and C support aging (Pt oxidation/dissolution/ripening, C oxidation, ...) under current-cycled operating conditions has never been explored. In this paper, on the basis of a combined theoretical and experimental approach, we investigate the long-term CO effect on PEFC performance and degradation. Firstly, on the basis of our previously published PEFC materials degradation models, we suggest that anodic CO poisoning could be used to mitigate the cathodic carbon catalyst-support corrosion phenomena and thus to enhance the MEA durability. Secondly, endurance experiments are performed on single fuel cells with current-cycled protocols representative of transport applications. The impact of CO on electrochemical transient response shows a reasonable agreement with simulated behaviors, and it is experimentally demonstrated that the impact of CO on the cell potential degradation rate is strongly dependent on the current-cycle mode. (C) 2009 Elsevier Ltd. All rights reserved.