The inactivation of spores of Bacillus atrophaeus and of Aspergillus niger using beams of argon ions, of oxygen molecules and of oxygen atoms is studied. Thereby, the conditions occurring in oxygen containing low pressure plasmas are mimicked and fundamental inactivation mechanisms can be revealed. It is shown that the impact of O atoms has no effect on the viability of the spores and that no etching of the spore coat occurs up to an O atom fluence of 3.5 × 1019 cm−2. The impact of argon ions with an energy of 200 eV does not cause significant erosion for fluences up to 1.15 × 1018 cm−2. However, the combined impact of argon ions and oxygen molecules or atoms causes significant etching of the spores and significant inactivation. This is explained by the process of chemical sputtering, where an ion-induced defect at the surface of the spore reacts with either the incident bi-radical O2 or with an incident O atom. This leads to the formation of CO, CO2 and H2O and thus to erosion.