The influence of fatigue cycling on the oxidation kinetic and crack initiation of a Cr–Mo steel has been studied. For this purpose, high temperature low cycle fatigue tests were performed in both the absence and presence of mechanical cycling. Then the number of cycles to crack initiation has been determined using two methods based on the evolution of the oxide penetration and the crack length, and the activation energy. Based on microscopic observations and experimental results, a new criterion assimilating the average thickness of the oxide layer to a microcrack is proposed. It appears that the number of cycles to crack initiation corresponds to a microcrack equivalent to the average size of the grain.