Scuffing failure generally occurs at oil film breakdown and large amount of metal-to-metal interaction between the contacting surfaces, where the role of surface roughness and lubricant becomes prominent. In order to evaluate the effect of surface roughness and lubricant on scuffing, scuffing simulation was carried out using contact mechanics and plasto-elastohydrodynamic lubrication model (MixedPEHL) by taking into account the plastic deformation in the contact area. The evolution of pressure, film thickness, contact area ratio, and subsurface effective plastic strain (EPS) was performed with three types of surface roughness and two different lubricants. Comparisons of pressure distribution, film thickness distribution, film thickness to surface roughness ratio (λ ratio), and contact area ratio were described to investigate the effect of surface roughness and lubricants on scuffing behavior. A better understanding on the effect of surface roughness and lubricant on scuffing processes was obtained through the research work.