The LiNi0.5−x Cu x Mn1.5−y Al y O4 (x = 0, 0.05, y = 0, 0.05) powders are synthesized by liquid co-precipitation and wet-milling. The doping effect on LiNi0.5Mn1.5O4 by Al3+, Cu2+, and Al3+/Cu2+ co-doping are investigated and compared in relation to physical and electrochemical characterization, namely, through X-ray diffraction, scanning electron microscopy, electronic conductivity, cyclic voltammetry and cycle tests. Results suggest that both Al3+ and Cu2+ doping effectively improve electrochemical performance of LiNi0.5Mn1.5O4, although the effect is different between the two cations. All doped samples exceed 95% capacity retention after 100 cycles at room temperature compared to 92% retention for the undoped sample. Moreover, co-doped LiNi0.45Cu0.05Mn1.45Al0.05O4 exhibits the best cyclic performance with slight superiority.