The primary aim of these interdisciplinary studies is to investigate the effect of surface carbon coating on the physico-chemical properties and toxicity of carbon-coated and noncoated copper and nickel nanoparticles (C-Cu, Cu, C-Ni, Ni NPs) in A549 alveolar epithelial cells. Compared to Cu NPs, C-Cu NPs exhibit protection against surface oxidation, tenfold higher cellular uptake, and fourfold lower release of soluble Cu. The toxicity of C-Cu NPs and Cu NPs is associated with pronounced damage to mitochondrial function and plasma membrane integrity, respectively. Compared to Cu and C-Cu NPs, Ni and C-Ni NPs are less toxic. These studies demonstrate that correlations can be drawn between physico-chemical properties and resultant toxicity of NPs as a function of surface carbon coating.