In this study, the fatigue performance of asphalt mixtures with high reclaimed asphalt pavement (RAP) content and rejuvenating agents (RA) has been investigated at the level of fine aggregate matrix (FAM) mix. Fatigue tests were conducted on four mixes: FAM without RAP, FAM with 25% RAP binder replacement, FAM with 25% RAP and two types of rejuvenators. Both the linear amplitude sweep (LAS) and conventional time sweep fatigue testing were used. The comparison between mixes with RAP and without RAP indicated that the addition of RAP results in a higher stiffness and faster damage rate as expected. Adding rejuvenators to the FAM mixes with RAP did not cause an appreciable reduction of stiffness. The incorporation of rejuvenators may improve the damage resistance and extend the fatigue life of FAM mixes with RAP; however, they were still inferior to the virgin FAM mix without RAP in terms of cracking resistance.