Carbon-supported Pt catalyst systems containing defect adsorption sites on the anode of direct methanol fuel cells were investigated, to elucidate the mechanisms of H2 dissociation and carbon monoxide (CO) poisoning. Density functional theory calculations were carried out to determine the effect of defect sites located neighboring to or distant from the Pt catalyst on H2 and CO adsorption properties, based on electronic properties such as adsorption energy and electronic band gap. Interestingly, the presence of neighboring defect sites led to a reduction of H2 dissociation and CO poisoning due to atomic Pt filling the defect sites. At distant sites, H2 dissociation was active on Pt, but CO filled the defect sites to form carbon π-π bonds, thus enhancing the oxidation of the carbon surface. It should be noted that defect sites can cause CO poisoning, thereby deactivating the anode gradually.