The anode flow rate of a proton exchange membrane (PEM) fuel cell involving Pt anode electrocatalyst is found to strongly influence the single cell performance when H-2 containing trace amounts of CO is used as the feed. The performance drops dramatically due to CO poisoning as the anode flow rate increases until a large overpotential is reached when it levels off. This effect of the flow rate on the extent of poisoning is found to be reversible and is explained as depending on the actual concentration of CO in the anode chamber which in turn depends on the feed content, the flow rate, and CO oxidation kinetics on Pt. Further, it is found that oxygen permeating across the PEM from the cathode side also appreciably affects the anode overpotential by providing another route for CO oxidation. A CO inventory model is provided that explains the observed phenomena in a PEM fuel cell operating with H-2/CO as anode feed and a cathode feed with different oxygen pressures.