Fast O2 scavenging can be achieved with the use of enzymatic O2 scavengers. The most commonly used is glucose oxidase coupled with catalase in the presence of glucose as a reducing agent, leading to effective O2 scavenging for many applications. It is generally compatible with electrochemical biosensors based on reductases, but typically incompatible with oxidase-based biosensors. The first issue is an overlap in substrate specificity between the oxidase used for O2 scavenging and the oxidase used for sensing. This problem can often be mitigated, given the vast biodiversity that offers a wide range of highly specific oxidases. The second, more challenging issue remains unresolved: while oxidases are generally specific to their substrate, they tend to be highly promiscuous with electron acceptors. The catalytic mechanism of oxidases typically follows a so-called ping-pong mechanism (Figure ), where the enzyme is first reduced by the substrate and then reoxidized, either by its natural electron acceptor (O2) or by artificial electron mediators designed to shuttle electrons in secondgeneration electrochemical biosensors. Consequently, artificial electron acceptors, such as Os-complexes or ferrocene derivatives commonly used in oxidase-based biosensors, may also accept electrons from the oxidase employed for O₂ scavenging. This can lead to shortcircuiting of the anodic electron transfer involved in the sensing function. Here, we develop the first universal enzymatic O2 scavenger that is compatible with oxidasebased electrochemical biosensors, utilizing alcohol oxidase and catalase. This system catalyzes the reaction between a reducing agent (paraformaldehyde) and O2 to yield water as the sole product from O2 reduction (Figure ). We selected alcohol oxidase as catalyst for O2 scavenging because it exclusively uses O2 as electron acceptor owing to a ternary-complex mechanism requiring simultaneous O2 and substrate binding in the catalytic active site for the substrate oxidation (Figure ). This unique characteristic among oxidases ensures that no other natural or synthetic electron acceptors can capture electrons from alcohol oxidase, conferring crucial specificity in O2 scavenging systems that is currently lacking in secondgeneration biosensors utilizing oxidases. A second useful feature of alcohol oxidase is that, in addition to catalyzing the oxidation of short-chain primary aliphatic alcohols to aldehydes and H₂O₂ using O₂, it also catalyzes the oxidation of formaldehyde to formate. Since formaldehyde is rapidly generated in situ from the hydrolysis of paraformaldehyde, we used the latter as a non-volatile precursor for the substrate of the alcohol oxidase. This greatly facilitates the handling and storage of the sensors for point-of-care applications. S is substrate and P is product. d) The O2 scavenger based on alcohol oxidase (AOx) oxidizes formaldehyde generated from the hydrolysis of paraformaldehyde to formate and thus reduces O2 to H2O2 which is further reduced to water through the combined reactions of catalase and AOx. AOx may use either formaldehyde as substrate producing formate or short chain, primary, aliphatic alcohols producing aldehydes. e) Random-order ternary complex mechanism of AOx, showcasing simultaneous docking of both oxygen and the alcohol substrate to realize highly specific oxygen scavenging.