Monocrystalline copper(II) oxide nanoparticles were made by scalable flame spray pyrolysis (FSP) and analyzed by X-ray diffraction (XRD), nitrogen adsorption (BET), transmission electron microscopy (TEM) and X-ray absorption near edge structure (XANES). Their primary particle diameter was closely controlled from 6 to 50 nm by varying the FSP conditions. Their electrochemical performance as Li-ion battery materials was tested in composite electrodes vs. Li-metal. Near theoretical specific charges were obtained for intermediate CuO sizes of 20 and 50 nm (d BET). In contrast, larger, commercially available CuO (d BET = 670 nm) exhibited significantly lower practical specific charge due to incomplete oxidation in the delithiation cycle as indicated by the remaining Cu and Cu2O by XRD and XANES analysis.