A non-stoichiometric calcium titanate CaTiO3-δ (CTO) was synthesized and used as oxygen reduction reaction co-catalyst (together with Pt/C) in direct methanol fuel cells (DMFCs). A membrane-electrode assembly (MEA), equipped with a composite cathode formulation (Pt/C:CTO1:1), was investigated in DMFC, using a 2 M methanol solution at the anode and oxygen at the cathode, and compared with an MEA equipped with a benchmark Pt/C cathode catalyst. It appears that the presence of the CTO additive promotes the oxygen reduction reaction (ORR) due to the presence of oxygen vacancies as available active sites for oxygen adsorption in the lattice. The increase in power density obtained with the CTO-based electrode, compared with the benchmark Pt/C, was more than 40% at 90 °C, reaching a maximum power density close to 120 mW cm−2, which is one of the highest values reported in the literature under similar operating conditions.