Proton exchange membrane fuel cells (PEMFCs) are attractive power plants for use in many applications, including portable power sources, electric vehicles, and on-site combined power/heat plants. Despite the advantages, one of the significant obstacles to PEMFC commercialization is the low tolerance to carbon monoxide (CO). Ideally, PEMFCs should use pure hydrogen fuel. However, because of the difficulties inherent in storing hydrogen onboard, there is an increasing interest in using hydrogen-rich gases produced by reforming hydrocarbon fuels. Fuel reformer produces hydrogen containing a small amount of CO. PEMFC performance degrades when CO is present in the fuel gas, referred to as CO poisoning. This paper presents the results of a novel PEMFC performance study using a pulsed heating device and the feeding channel pressure swing method to mitigate the CO poisoning problem. The effectiveness of these strategies is demonstrated through simulation and experimental work on a single cell. By applying a transient localized heating to the catalyst layer while maintaining the PEMFC membrane at a normal temperature (below ) and by using the feeding channel pressure swing, significant enhancement in the carbon monoxide tolerance level of PEMFCs was found. These approaches could potentially eliminate the need for an expensive selective oxidizer. The CO poisoning process is generally slow and reversible. After applying pulsed heating, the transient high temperature in the catalyst layer could help the recovery of the PEMFC from CO poisoning. By using feeding channel pressure swing, oxygen can easily diffuse into the membrane electrode assembly (MEA) from the outlet port and promote a quick recovery. Using these operational strategies, a PEMFC could operate continually using a high CO concentration fuel.