In this work, we made an attempt to understand the influence of the annealing treatment on CO sensing with tin dioxide based sensors. As a first step, the surface of tin dioxide powders and of sensitive layers based on them has been characterised by means of the IR studies; it was shown in this way that at the surface of thick film SnO 2 based sensors the structure of hydroxyl groups is similar to the one found at the surface of SnO 2 powders, independent on the sensors’ annealing temperature. Afterwards, the CO reaction with sensors annealed at 500 and 700 °C has been investigated by simultaneous electrical and infrared studies (DRIFTS) in operando conditions (air, 200–400 °C). It was concluded that the final annealing temperature influences the concentration of the reactive sites for oxygen ionosorption, which finally determines the main CO reaction route and thus the sensor signal.