The oxidation of alcohols and ethers by O₂ with the enzyme laccase, mediated by the stable N‐oxyl radical TEMPO, affords carbonylic products. An ionic mechanism is proposed, where a nucleophilic attack of the oxygen lone‐pair of the alcohol (or ether) onto the oxoammonium form of TEMPO (generated by laccase on oxidation) takes place leading to a transient adduct. Subsequent deprotonation of this adduct α to the C−O bond leads to the carbonylic product. Additional mechanistic considerations for the laccase‐mediated oxidation of ethers and thioethers are offered. The proposed mechanism is supported by: (i) investigating the inter‐ and intramolecular selectivity of oxidation with appropriate substrates, (ii) thermochemical considerations, and (iii) attempting a Hammett correlation for the oxidation of a series of 4‐X‐substituted benzyl alcohols, wherein a shift of the rate‐determining step as a function of the 4‐X‐substituent results. Based on the above points, the lack of mediation efficiency of another stable N‐oxyl radical (viz., IND‐O^·) can be explained. (© Wiley‐VCH Verlag GmbH & Co KGaA, 69451 Weinheim, Germany, 2002)