The effects of intrinsic cation disorder and electron-deficient substitution for La1-xSrxCo0.5Mn0.5O3-delta (LSCM, x = 0, 0.5, and 0.75) on oxygen vacancy formation, and their influence on the electrochemical properties, were revealed through a combination of computer simulation and experimental study. First-principles calculations were first performed and found that the tendency of the oxygen vacancy formation energy was Mn3+-O*-Mn4+ < Co2+-O*-Co3+ < Co2+-O*-Mn4+, meaning that antisite defects not only facilitate the formation of oxygen vacancy but introduce the mixed-valent transition-metal pairs for high electrical conductivity. Detailed partial density of states (PDOS) analysis for Mn on Co sites (Mn-Co) and Co on Mn sites (Co-Mn) indicate that Co2+ is prone to being Co3+ while Mn4+ is prone to being Mn3+ when they are on antisites, respectively. Also it was found that the holes introduced by Sr tend to enter the Co sublattice for x = 0.5 and then the O sublattice when x = 0.75, which further promotes oxygen vacancy formation, and these results are confirmed by both the calculated PDOS results and charge-density difference. On the basis of microscopic predictions, we intentionally synthesized a series of pure LSCM compounds and carried out comprehensive characterization. The crystal structures and their stability were characterized via powder X-ray Rietveld refinements and in situ high-temperature X-ray diffraction. X-ray photoelectron spectroscopy testified to the mixed oxidation states of Co2+/Co3+ and Mn3+/Mn4+. The thermal expansion coefficients were found to match the Ce0.8Sm0.2O2-delta electrolyte well. The electrical conductivities were about 41.4, 140.5, and 204.2 S cm(-1) at doping levels of x = 0, 0.5, and 0.75, and the corresponding impedances were 0.041, 0.027, and 0.022 Omega cm(2) at 850 degrees C, respectively. All of the measured results testify that Sr-doped LaCo0.5Mn0.5O3 compounds are promising cathode materials for intermediate-temperature solid oxide fuel cells.