Apart from large surface areas, low activation energies are essential for efficient reactions, particularly in heterogeneous catalysis. Here, we show that not only the size of nanoparticles but also their detailed morphology can crucially affect reaction kinetics, as demonstrated for mass-selected, soft-landed, and oxidized cobalt clusters in a 6 nm to 18 nm size range. The method of reflection high-energy electron diffraction is extended to the quantitative determination of particle activation energies which is applied for repeated oxidation and reduction cycles at the same particles. We find unexpectedly small activation barriers for the reduction reaction of the largest particles studied, despite generally increasing barriers for growing sizes. We attribute these observations to the interplay of reaction-specific material transport with a size-dependent inner particle morphology.