Infrared spectroscopy of adsorbed CO has been used to characterize the effect of adsorbed methanol on the Lewis acidity of 4 nm rutile TiO2 nanoparticles. Measurements of CO absorbance and vibrational frequency have revealed that CO adsorbs primarily at one class of Lewis acid sites on clean TiO2 particles, where evidence for lateral interactions between neighboring molecules suggests dense coverage occurs near saturation. The response of the CO infrared in and frequencies to methanol exposure has shown that methanol uptake occurs primarily at the Lewis acid sites and through hydrogen bonding to surface OH groups. These surface sites appear to be responsible for driving both molecular and dissociative adsorption of methanol on the titania. Most importantly, these studies have revealed that the parent methanol and associated methoxy products lower the Lewis acidity of neighboring sites on TiO2 nanoparticles.