The electrochemical properties of substituted LiNi0.5Mn1.5-xMxO4 spinels at high potential (>4V vs Li+/Li) have been investigated for M = Ti and Ru, in order to determine the role of the tetravalent cation in such systems where nickel is a priori the only electroactive species. These systems are found to form extended solid solutions (up to x = 1.3 and x = 1.0 for Ti and Ru, respectively) that were characterized by X-ray diffraction and Raman spectroscopy. Titanium substitution induces a drastic decrease in high potential electrochemical capacity, whereas the capacity is maintained and the kinetics are even improved in the presence of ruthenium. These results are completed by new results on the Li4-2xNi3xTi5-xO12 spinel system, which shows not any high potential activity in spite of the presence of up to 0.5 Ni2+ per spinel formula unit on the octahedral site. Taking into account previous data on LiNi0.5Ge1.5O4, we clearly show that even if the tetravalent cation does not participate in the overall redox reaction, electrochemical activity is only possible when nickel is surrounded by tetravalent cations able to accept a local variation of valence (Mn, Ru), whereas full-shell cations such as Ti4+ and Ge4+ block the necessary electron transfer pathways in the spinel oxide electrode. (C) 2010 Elsevier Ltd. All rights reserved.