The photochemistry of six N3-(3-fluoro-4-dialkylaminophenyl)-oxazolidinones known for their antimicrobial activity has been examined. All of these compounds are defluorinated in water (Φdec ≈ 0.25) and in methanol (Φdec ≈ 0.03), reasonably via the triplet. The chemical processes observed are reductive defluorination and solvolysis, depending on the structural variation introduced (thus, tethering the dialkylamino group to the aromatic ring and introducing a highly polar group in the oxazolidinone moiety have an effect). A likely mechanism involves the fragmentation of the C–F bond yielding the corresponding triplet phenyl cation. This intermediate either is reduced or, under appropriate conditions, intersystem crosses to the singlet state that adds the solvent. These data demonstrate a sizeable photodecomposition of these drugs that causes a decrease in the therapeutic activity. Furthermore, the likely formation of phenyl cations may cause a photogenotoxic effect.