The role of Sn on the catalytic activity for CO and formic acid oxidation is studied by comparing the activities of differently treated PtSn/C and Pt/C catalysts. The catalysts are prepared by a microwave-assisted polyol synthesis method. As revealed by scanning tunneling and transmission electron microscopic (STM and TEM) characterization, the outcomes of the synthesis procedure for both Pt and PtSn are small particles, ∼1.5 nm in diameter. Upon deposition on the carbon support, the particle size increases to ∼2.5 nm due to sintering. X-ray diffraction (XRD) analysis shows that PtSn/C has a low alloying degree and is mainly composed of Pt and Pt3Sn phases. The remaining Sn is present in the form of very small tin oxide particles. Different surfaces are obtained by double-layer, oxide, and CO annealing of the Pt/C and PtSn/C catalysts and by modifying the CO-annealed surfaces with irreversibly adsorbed tin, Snirr. The presence of Sn in any form (oxide, alloyed, or Snirr) on the surface shifts the onset potential for the CO oxidation negatively by more than 0.4 V in comparison to equivalently treated Pt/C catalysts. For the CO-annealed PtSn/C catalyst, a so-called skeleton structure, Sn is present only in the subsurface layers. The subsurface Sn has a mild effect on the CO activity, and hence the onset potential is only marginally shifted to cathodic potentials by ∼50 mV compared to that on Pt/C. The formic acid oxidation is enhanced at any of the PtSn/C surfaces with Sn in the surface layer. The activity enhancement is explained by a reduced CO poisoning of the surface Pt sites. As a consequence, the current is not entering plateau as on the Pt/C catalysts. Furthermore, the skeleton PtSn/C is ∼2 times more active than similarly treated Pt/C. The results have been substantiated and explained by comprehensive density functional theory (DFT) simulations. The DFT results indicate that the increased oxidation rates are not only due to surface Sn but also due to a weakened CO binding in the vicinity of the surface SnOHx moieties and SnO2 particles.