Cationic and anionic doping in LiNi0.5Mn1.5O4 has been prepared via a solid state method. The effect of substitution on the structure, morphology, and electrochemical properties were investigated. The XRD and Raman results indicate that all synthesized materials have a phase-pure spinel structure with a space group of Fd3m and no obvious impurity phase peaks. Excellent cycle life is measured for these 5V Cr and (or) F-doped electrodes. When the charge/discharge rate returns to 1C after the test of rate capability (0.1-5C), the capacity can be completely recovered and the capacity retention is about 98.6%, 98.8% and 96.2% after 100 cycles for LiNi0.45Cr0.05Mn1.5O4, LiNi0.45Cr0.05Mn1.5O3.9F0.1 and LiNi0.5Mn1.5O3.9F0.1, respectively. Furthermore, rate capability is greatly influenced by the relative content of Mn3+. Cr and (or) F substitutions supply an efficient process to tune the Mn3+ concentration in the lattice.