Understanding the comprehensive factors of oxidation behaviors and revealing their contribution to fatigue failure is of great importance. The low-cycle fatigue (LCF) coupled oxidation behavior of a novel low-cost third generation Ni-based single crystal superalloy with only 3 wt% of Re at 800 ℃ and 1000 ℃ was studied in the present work. The results indicated that oxidation-induced crack initiation was specifically responsible for the drastic reduction in LCF life at high temperatures, as opposed to the unobvious creep deterioration and the inferior fatigue damage via crack propagation in slow model-I. However, it was found that the preferential spallation of the weakly bonded (Ni, Co)O layer was beneficial in suppressing crack initiation. In terms of crack propagation, the proceeding oxidation of nearby fatigue cracks could boost dislocation recovery process, which thereby improved the toughness of the surrounding substrate to decelerate crack propagation. Noteworthy, a specific asymmetric oxidation phenomenon in single crystal alloy was identified for its required cyclic crystal rotation in one single grain. Importantly, guidance for chemical composition optimization was proposed that future efforts should be made to reduce oxidation damage during fatigue deformation by lowering oxidation kinetics and increasing the bonding strength of oxide layers.