Oxygen loss can lead to high-capacity Li2MnO3-based lithium-rich layered cathodes. Substitution of Mn with other transition metals (Ti and Co) significantly affects the amount of oxygen loss and capacity during the first charge/discharge cycle. An explanation of these results is provided with density functional theory (DFT+U) electronic structure calculations. Oxygen is found to bind more strongly to Ti and more weakly to Co. The influence of the substitution is attributed to changes of the band gap. Ti lifts the nonbonding band and increases the band gap of the compound, thus raising the energy required to redistribute the electrons released upon oxygen loss. Co lowers the nonbonding band and facilitates oxygen loss.