The bond activation of ethanol by the ground-state Ni+(2D) in the gas phase has been theoretically investigated using density functional theory. The approach of Ni+ towards ethanol could form five different Ni+–ethanol adducts, which correspond to Ni+ interaction through the O atom and C–H bonds, respectively. The O attached complexes are much more stable than that with Ni+ interaction through the C–H bonds. Extensive conversions into each other could occur readily for these encounter complexes. The loss of H2O and C2H4proceeds via three pathways, i.e., Ni+ insertion into the polar C–O bond through the O attached Ni+–ethanol complexes, initial Cβ–H activation via the Ni+–ethanol complex with Ni+ interaction through the methyl C–H bonds, and electrophile-inducted one-step syn-elimination through the Ni+–gauche-ethanol complex, and the last one is the most favorable. The loss of H2 is less favorable, because all mechanisms involve high activation barriers, while the initial Cα–H bond activation of ethanol by Ni+ through the O attached Ni+–ethanol complexes is the most favorable.