The relationship between the catalytic activity and the size was studied in operando in the case of gold nanoparticles on TiO₂(110) model catalyst during carbon monoxide oxidation. The geometrical parameters, the shape and the dispersion of the particles on the oxide support were examined in detail. The catalytic activity was found optimum for a nanoparticle diameter of about 2 nm and a height of six atomic monolayers. Above the maximum, it fits a power law of the diameter D^{−2.4 ± 0.3}. This indicates that the low-coordinated sites play a major role in the catalytic activity, however such a model still fails to explain the activity maximum. The nanoparticle sintering was also investigated since it is suspected of being responsible for the decrease of the catalyst activity in the course of time. It was clearly observed for particles with a size around the maximum of activity and smaller. At the very beginning of the CO conversion into CO₂, the sintering is strongly activated. The nanoparticles mobility is dependent upon the TiO₂(110) surface direction under consideration: it is higher along the [001]_TiO2 than along the [1–10]_TiO2. Then, the sintering greatly slows down. This could be explained by a nanoparticles’ pinning at the step edges. The thermal energy released by the exothermic CO oxidation reaction was evaluated and it suggests that the sintering results from a more complex process than from a reaction-induced local heating.