Durability represents one of the major barriers to the progress of the Proton Exchange Membrane Fuel Cells (PEMFCs). To elucidate the degradation of these devices, it is important to understand the issues regarding the long-term operation of PEMFCs. Thus, in this work it was analyzed the influence of the operational parameters such as relative humidity, cell temperature and the reactant flow rates on the long-term performance through experiments of 500 hours at steady state. It was observed that the degree of humidification strongly influences on the long-term performance. The test which presented the lowest global loss of performance (with both irreversible and reversible losses) was the one with the temperatures of the humidifiers and cell all set as 75??C and the reactants flow rates set as 300 and 200 ml.min-1 for the H2 and O2, respectively. Therefore, the water management is a key point in order to obtain better performances in long-term operation of PEMFCs.