LiNi0.5−x Co2x Mn1.5−x O4 (0≤2x ≤0.2) was prepared by a spray dry process and comparative studies were carried out between the as-prepared series and the series re-annealed in O2. The cobalt substitution resulted in significant structural and electrochemical variations, such as the transformation of the space group from P4332 to F d 3 ¯ m , the increase in the occupancy of cobalt in the tetrahedral sites, and the change in the shape of the charge and discharge profiles, which are related to the progressive oxygen loss. Moreover, an improved rate capability and cyclic performance at high rate was observed for the sample with 2x ≥0.1.