In 2 O 3 -based gas sensing devices were processed by screen printing In 2 O 3 powders obtained by spray pyrolysis. The acetone (0.75-5 ppm concentration) sensing properties were measured at 250°C at several humidity values. The devices could provide an appreciable response even to the lowest acetone concentrations, and it was found that increasing humidity resulted in decreased response up to 30% RH (atmosphere @ 26°C), after which no more changes were observed. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was employed for studying in operando the surface chemistry of the devices. It was evidenced that the surface could be reduced and re-oxidized in N 2 and 1000 ppm O 2 concentration, respectively. DRIFTS study in H 2 , D 2 and H 2 O/D 2 O demonstrated that the In 2 O 3 surface was amenable to hydroxylation, enhanced by newly formed oxygen surface sites, and to reduction by humidity. DRIFTS studies in acetone evidenced that the hydroxylated In 2 O 3 surface decomposes acetone resulting in hydroxyl consumption and adsorbed acetates The overall resulting consumption of surface oxygen is at the basis of the observed conductance increase in the gas-sensing tests. The sensing mechanism is therefore not based onto surface combustion of acetone.