It has been proposed (J. Phys. Chem. B 2011, 115, 2671) that the ammonium group is involved in the gas-phase reaction of protonated methionine (MetH(+)) with singlet oxygen O-1(2)., yielding hydrogen peroxide and a dehydro compound of MetH(+) where the -NH3+ transforms into cyclic -NH2-. For the work reported, the gas-phase reaction of protonated N-acetylmethionine (Ac-MetH(+)) with O-1(2) was examined, including the measurements of reaction products and cross sections over a center-of-mass collision energy (E-col) range from 0.05 to 1.0 eV using a guided-ion-beam apparatus. The aim is to probe how the acetylation of the ammonium group affects the oxidation chemistry of the ensuing Ac-MetH(+). Properties of intermediates, transition states, and products along the reaction coordinate were explored using density functional theory calculations and Rice-Ramsperger-Kassel-Marcus (RRKM) modeling. Direct dynamics trajectory simulations were carried out at E-col of 0.05 and 0.1 eV using the B3LYP/4-31G(d) level of theory. In contrast to the highly efficient reaction of MetH(+) + O-1(2) the reaction of Ac-MetH(+) + O-1(2) is extremely inefficient, despite there being exoergic pathways. Two product channels were observed, corresponding to transfer of two H atoms from Ac-MetH(+) to O-1(2) (H2T), and methyl elimination (ME) from a sulfone intermediate complex. Both channels are inhibited by collision energies, becoming negligible at E-col > 0.2 eV. Analysis of RRKM and trajectory results suggests that a complex-mediated mechanism might be involved at very low E-col, but direct, nonreactive collisions prevail over the entire E-col range and physical quenching of O-1(2) occurs during the early stage of collisions.