The electrochemical reactivity of tailor-made or CuO powders prepared according to the polyol process was tested in rechargeable Li cells. To our surprise, we demonstrated that CuO, a material well known for primary Li cells, and could reversibly react with 1.1 Li and 2 Li ions per formula unit, respectively, leading to reversible capacities as high as 400 mAh/g in the 3-0.02 V range. The ability of copper oxide-based Li cells to retain their capacity upon numerous cycles was found to be strongly dependent on the particle size, and the best results (100% of the total capacity up to 70 cycles) were obtained with 1 μm and CuO particles. Ex situ transmission electron microscopy data and in situ X-ray experiments show that the reduction mechanism of by Li first involved the formation of Cu nanograins dispersed into a lithia matrix, followed by the growth of an organic coating that partially dissolved upon the subsequent charge while Cu converted back to nanograins. We believe that the key to the reversible reactivity mechanism of copper oxides or other transition metal oxides toward Li is the electrochemically driven formation of highly reactive metallic nanograins during the first discharge, which enables the formation-decomposition of upon subsequent cycles.© 2001 The Electrochemical Society. All rights reserved.