The particle size effect observed on the performance of Pt/C electrocatalysts toward the methanol oxidation reaction (MOR) has been investigated with differential electrochemical mass spectrometry (DEMS). The investigation has been conducted under both potentiodynamic and potentiostatic conditions as research on methanol electrochemical oxidation is closely related to interest in direct methanol fuel cells. The particle size effect observed on the MOR is commonly regarded as a reflection of different Pt-CO and Pt-OH bond strengths for different particle sizes. This work focuses mainly on the mechanism of methanol dehydrogenation on platinum which is central to the problem of the optimization of the efficiency of methanol electro-oxidation by favoring the CO(2) formation pathway. It was found that the partitioning of the methanol precursor among the end products on supported platinum nanoparticles is strongly dependent on particle size distribution. Also, it is postulated that the coupling among particles of different sizes via soluble products must be considered in order to understand the particle size effects on the observed trends of product formation. An optimum particle size range for efficiently electro-oxidizing methanol to CO(2) was found between 3 and 10 nm, and loss in efficiency is mostly related to the partial oxidation of methanol to formaldehyde on either too small or too large particles. The possible reasons for these observations are also discussed.