Pb quantum well films with atomic-scale uniformity in thickness over macroscopic areas were prepared on Si(111)-7×7 surfaces. As a probe molecule, O2 was used to explore the effect of electron confinement in the metal films on the surface reactivity. X-ray photoelectron spectroscopy results showed clear oscillations of oxygen adsorption and Pb oxidation with the thickness of the Pb films. The higher reactivity to O2 on the films with 23 and 25 ML Pb has been attributed to their highest occupied quantum well states being close to the Fermi level (EF) and the high density of the electron states at EF (DOS-EF), as evidenced by the corresponding ultraviolet photoelectron spectroscopy. A dominant role of DOS-EF was suggested to explain the quantum modulation of surface reactivity in metal quantum well films.