The mechanism of nitrite reduction at the Cu(II) center of both copper nitrite reductase and a number of corresponding synthetic models has been investigated by using both QM/MM and cluster calculations employing density functional theory methods. The mechanism in both cases is found to be very similar. Initially nitrite is bound in a bidentate fashion to the Cu(II) center via the two oxygen atoms. Upon reduction of the copper center, the two possible coordination modes of the protonated nitrite, by either nitrogen or a single oxygen atom, are close in energy, with nitrogen coordination probably preferred. Further protonation of this species leads to N-O bond cleavage, and an electron transfer from the Cu(I) center to the N-O+ ligand, resulting in loss of NO and regeneration of the resting state of the enzyme having a bound water molecule.