Interconnects are a key component of integrated circuits (IC) and play a major role in the speed and power consumption of an IC. While surface roughness is essential for ensuring adhesion to other components in an IC, it also increases electron scattering at the surface, which can dramatically increase resistivity. Barrier layers have been introduced to mitigate the effect of rough Cu surfaces, but explanations of their behavior are varied. Using a combination of density functional theory (DFT) and the non-equilibrium Green’s function technique in conjunction with DFT (NEGF-DFT), our work aims to identify key tradeoffs between surface roughness profiles and electronic performance in copper wire interconnects, and how barrier layer atoms affect conductance across the Cu surface. We find that by removing atoms from the surface, the current allowed across the film is reduced to that of a thinner pristine film, but that as the voltage is increased the defected film recovers some of the conductance of the pristine system. By replacing the vacancy with a substituent atom (Ag, Al, Au, Co, Ir, Ni, Pd, Rh, Sn, Zn, Zr) we find that conductance across the film is intimately related to the periodic table group of the substituent atom relative to Cu.