On the route towards higher energy densities of lithium ion batteries (LIBs) for electromotive applications, the low capacity of state-of-the-art cathode materials is still a limiting factor. Lithium-rich layered oxides (LLOs), a composite of layered LiMO2 (M = Ni, Co, Mn) and Li2MnO3, are a promising material class, which exhibit high discharge capacities based on additional anionic redox activity but still suffer from oxygen release and correlated structural instability. In order to overcome these issues, which are mostly related to the Li2MnO3 parent structure, doping is a common strategy. In this study, the effects of different cation dopants on manganese and lithium sites of the Li2MnO3 structure were systematically studied using first-principles calculations based on density functional theory (DFT). By using cluster expansion methods the thermodynamically stable ground states of doped and delithiated structures were calculated. We show that the dopants have a severe influence on the delithiation process, a fact that is often neglected in theoretical studies of doped structures. Multivalent dopants on lithium sites, like Al3+ and Ti4+, have a strong effect on the electronic structure as well as on the initial redox potential of the material. Moreover, enhanced metal–oxygen bonding and a decreased oxidation of the oxygen anions during delithiation are observed which indicate a reduction of both, the irreversible release of oxygen as well as unwanted structural changes.