Abstract Recent evidence has shown that low temperature neutral–neutral reactions may be more important in the chemistry of the interstellar medium than originally realized. In this paper, possible chemical reactions among known carbon-, hydrogen- and oxygen-bearing interstellar neutral molecules have been explored theoretically using density functional theory and coupled cluster methods. Potential energy surfaces have been generated for molecules with the overall stoichiometries C3H2O, C3H3O, and C4H3O. For each surface, the geometries of the transition states along various pathways have been determined. The most probable pathways of reaction and the resultant products are discussed. Reactions involving the hydroxyl radical and various carbon-containing species have been specifically examined as they are the most prolific producers of complex organic compounds. It is demonstrated that the hydroxyl radical may be responsible for infusing oxygen into a host of interstellar organic molecules. The generation of small carbon oxides from carbon clusters and HCO has also been explored and the absence of HCnO (n > 1) species in the interstellar medium rationalized.