Air contaminants can have detrimental effects on the performance and durability of proton exchange membrane (PEM) fuel cell vehicles. This research focuses on the experimental investigation of the effect of nitrogen monoxide (NO) in the cathode gas stream, which provokes a cell voltage decrease due to the partially reversible adsorption of NO on the platinum catalyst. The concentration and exposure time of NO in the cathode gas stream are varied at selected constant current densities and load ramps to assess the effects throughout the fuel cell system operating range. The results show the cell voltage loss in the presence of NO and reveal a near-catalyst saturation with increased injected NO mass. Additionally, several voltage recovery and mitigation strategies are introduced and discussed by presenting conclusions about the general effect of NO on a fuel cell system in operation. The most promising recovery strategy for fuel cell systems is identified, and the overall system degradation is discussed. All experiments are performed in a test bed environment on a 25 kW low-temperature fuel cell system via controlled injection of NO into the cathode gas stream.