The oxygen that is observed in the Solar System today is a remnant of the interstellar oxygen that was in the dense molecular cloud that collapsed to form the Solar System. While the chemical evolution of the Galaxy has progressed since then, processes in the interstellar medium (ISM) that involve oxygen are relevant to the origins of oxygen in the Solar System. Oxygen in the ISM can be found as neutral or ionized atomic gas and as a constituent of molecular gas, volatile ices, and refractory minerals in dust, with the dominant state depending on the specific environment. The gas-phase abundance of atomic oxygen is well-known in the diffuse ISM that fills most of the Galaxy’s volume, but the state of oxygen in denser environments is poorly understood. The ISM abundances of isotopes of oxygen other than 16O cannot be easily determined due to observational constraints. Oxygen in interstellar dust is primarily found in the form of silicates that are created in evolved stars and then ejected into the ISM before being incorporated into the formation of new solar systems. Some of the important unknowns concerning oxygen in the ISM include the “cosmic” (i.e., total) abundance of oxygen, the abundance of oxygen in dust, and the details of dust grain processing in the ISM.