NiCu single atom alloy (SAA) nanoparticles supported on silica are reported to catalyze the non-oxidative dehydrogenation of ethanol, selectively to acetaldehyde and hydrogen products by facilitating the CH bond cleavage. The activity and selectivity of the NiCu SAA catalysts were compared to monometallic copper and to PtCu and PdCu single atom alloys, in a flow reactor at moderate temperatures. In-situ DRIFTS showed that the silica support facilitates the OH bond cleavage of ethanol to form ethoxy intermediates over all the supported alloy catalysts. However, these remain unreactive up to 250 °C for the Cu/SiO2 monometallic nanoparticles, while in the NiCu SAA, acetaldehyde is formed at much lower temperatures, below 150 °C. In situ DRIFTS was also used to identify the CH activation step as the rate determining step of this reaction on all the copper catalysts we examined. The presence of atomically dispersed Ni in Cu significantly lowers the CH bond activation barrier, whereas Pt and Pd atoms were found less effective. This work provides direct evidence that the CH bond cleavage is the rate determining step in ethanol dehydrogenation over this type catalyst.