In this work, we investigate the influence of oxygen non-stoichiometry on the characteristics of LiNi0.8Co0.1Mn0.1O2 cathode material. Among the investigated samples, the level of Ni/Li disorder in the bulk and the thickness of auto-generated layer on the surface share the same trend as the amount of oxygen loss in LiNi0.8Co0.1Mn0.1O2 materials. It indicates that the aforementioned key structural instabilities should be tightly related to the oxygen defects and the induced structural relaxation. As a consequence of structural entirety, the sample with the least defects presents the highest discharge capacity (192.9 mAhg−1 at 0.1C), the best rate capability (160.1 mAhg−1 at 5C), and the most stable cyclibility (89.9% at 200th). Our results demonstrate that oxygen deficiency plays a key role to determine the electrochemical performance of high-nickel cathode materials.