The influence of cationic substitutions on the ease with which oxygen loss occurs from lithium-rich layered oxide cathodes during first charge has been studied with three series of samples: LiLi0.33Mn0.67−x Ti x O2 (0 ≤ x ≤ 0.67), LiLi0.2Mn0.54−x Ti x Ni0.13Co0.13O2 (0 ≤ x ≤ 0.27), and LiLi0.2Mn0.60−x Ti x Ni0.20O2 (0 ≤ x ≤ 0.40). The lattice parameters and cell volume increase monotonically with the substitution of a larger Ti4+ for Mn4+, indicating the formation of solid solutions. It is found that substitution of Ti4+ for Mn4+ decreases the degree of oxygen loss and consequently the charge and discharge capacity values, while substitution of Co3+ for (Mn0.5 4+Ni0.5 2+) increases the oxygen loss and consequently the charge and discharge capacity values. While the former is attributed to a stronger binding of oxygen to Ti and a decrease in the metal−oxygen covalence due to a larger charge transfer gap between the Ti3+/4+ 3d and O2− 2p bands, the latter is attributed to a weaker binding of oxygen to Co and an increase in the metal−oxygen covalence due to an overlap of the Co3+/4+ t2g band with the top of the O2− 2p band.