The poisoning of platinum electroactive surfaces by the adsorption of CO is a critical hindrance for the development of fuel cells. Combining Pt with (hydrous) ruthenium oxide has been shown to enhance the CO electrooxidation reaction on the electrocatalyst. However, how the co-catalyst surface provides oxygenated species to remove CO adsorbed on platinum is still an undiscussed matter. Here we show that an indispensable intermediate form of RuO2, catalyzed by Pt, is responsible for the removal of CO on Pt at low potential. In order to unravel the synergetic effect of ruthenium oxide and platinum towards CO electro-oxidation, ruthenium oxide nanosheets (RuO2(ns)) with monoatomic thickness were deposited onto the surface of polycrystalline Pt, glassy carbon and polycrystalline Au rotating disk electrodes. Combined with the well-defined electrochemical behavior of RuO2(ns), these model electrodes enabled to investigate both (i) the synergetic effect of ruthenium oxide towards the electro-oxidation of CO on Pt and (ii) the influence of the metal substrate (Pt or Au) towards the electrochemical behavior of RuO2. When deposited on the smooth Pt surface, RuO2(ns) were found to fully interact as a co-catalyst for the electro-oxidation of (monolayer adsorbed and bulk) CO on Pt, without blocking the electroactive surface of Pt. The addition of RuO2(ns) lead to two distinct synergetic effects for the bulk electro-oxidation of CO on Pt. Upgrading the general understanding, an interdependency between RuO2 and Pt is observed for the 'low potential' electro-oxidation of bulk CO (onset at 0.65 V vs. RHE).