Bitumen fatigue resistance is critical to determine the overall fatigue performance and service life of asphalt pavements. However, the mechanisms responsible for fatigue damage of bitumen have previously not been well understood. Molecular dynamics (MD) simulation has recently emerged as a powerful computer-aided numerical technique to model the microscopic failure behaviours in materials. This study aims to use the MD method to investigate the molecular origin of bitumen fatigue damage. The molecular models of the virgin and aged PEN70/100 bitumen were firstly constructed based on their saturate, aromatic, resin and asphaltene (SARA) four fractions. An MD equilibrium was run on the developed bitumen models with the assigned interatomic potentials. Following an MD-based tensile simulation, a strain-controlled fatigue simulation was performed to study the nanostructure and damage behaviours of the virgin and aged bitumen under fatigue loading by calculating the stress-strain response, potential energy, molecular structure and nanovoid volumes. Furthermore, a rheometer measurement was also conducted to characterise the fatigue damage of the bitumen directly by a crack length at the macroscale. Results indicate that the bitumen molecules become unfolded and tend to align along the loading direction when fatigue loading was applied. The change in the molecular configuration helped the molecular chains move closer together and thus contributed to the reduction of the intermolecular interactions including the van der Waals and Coulombic energies. With the increasing load cycles, nanovoids were formed and grew in the bitumen through molecular rearrangement and movement, leading to microscopic fatigue damage of the bitumen. It was found that the aged bitumen produced more severe fatigue damage than the virgin bitumen, which was indicated by the MD-based nanovoid volume at the molecular scale and the DSR-based crack length at the macroscale. The findings from MD simulation provide a fundamental understanding of the molecular origin of fatigue damage, that cannot be experimentally detected for bitumen materials.@en