Interactions between sulfur and Ni1-xCux (x = 0.00, 0.25, 0.50, 0.75, and 1.00) were examined by a first-principles analysis based on density functional theory (DFT) calculations to provide a scientific basis for intelligent design of sulfur-tolerant anode materials for solid oxide fuel cells (SOFCs). Examination of slab models with three and five atomic layers for Ni and Cu (1 1 1) surfaces indicates that sulfur species may adsorb on four types of sites: atop, bridge, hcp hollow, and fcc hollow, among which the fcc-hollow centers are the most energetically favorable. The adsorption energy of sulfur on Ni is approximately 20% higher than that on Cu for both unrelaxed and relaxed five-layer surface models, which is qualitatively in good agreement with experimental observations. Using two active sites at three-fold hollow sites, the adsorption energy for sulfur on Ni1-xCux is predicted as a function of the alloy composition. Alloying Ni with Cu improves sulfur tolerance, however not to the degree of pure Cu.