Constant amplitude fatigue tests at R=0.1, conducted on the aircraft aluminum alloy 2024 T3, have revealed an appreciable surface hardness increase of the alloy at the nano- and meso-scale during fatigue. The observed surface hardness changes could be monitored with confidence by means of nanoindentations. The degree of hardening increases with increasing number of fatigue cycles following exponential relations. With increasing fatigue stress level degree of hardening increases as well. The observed results provide a basis for developing concepts to early detect and also monitor fatigue damage accumulation in aluminum aircraft structures based on measurements of the material’s hardness changes by means of nanoindentations.