<p>Redox flow battery (RFB) employing oxygen as active material is a promising system because this oxygen can replace expensive conventional active materials. However, its practical application is limited due to the high overpotential of reactions involving oxygen and the necessity of continuous oxygen supply. To overcome the difficulties, in this study, new RFBs using redox reaction of mediator and electrochemical oxygen evolution reaction (OER) are suggested. Here, oxygen acts as a self-sustaining active material for catholyte operating without its external supply and anthraquinone-2,7-disulfonate (AQDS) is employed as a redox mediator to reduce the high overpotential of oxygen reduction reaction, while iron-2,2-bis(hydroxymethyl)-2,2’,2’-nitrilotriethanol complex (Fe(BIS-TRIS)) is considered as the active material for anolyte. A nickel-electrodeposited heat-treated graphite felt (Ni-HGF) electrode is further introduced to simultaneously facilitate the OER and redox reaction of AQDS mediator in cathode. Electrochemical analysis indicates that the Ni-HGF electrode lowers the potential required for oxygen evolution and provides suitable conditions for AQDS-mediated redox reactions, enabling continuous in situ generation and utilization of oxygen during cycling. As a result, in RFB single cell employing Ni-HGF electrode, its discharge capacity after 200 cycles (746&#xa0;h) (2.34 Ah L^− 1) is well preserved compared to its initial capacity of 2.55 Ah L^− 1. Furthermore, additional oxygen injection does not affect the discharge capacity, indicating that a sufficient amount of oxygen is continuously generated via OER during charging step and such generated oxygen is subsequently utilized during discharging step. This work proves a viability of a self-sustaining oxygen-based RFB that can operate without external oxygen supply, providing a new strategy for establishing a low-cost energy storage system.</p>