The flavonoids constitute a large group of polyphenolic phytochemicals with antioxidant properties in vitro. The interactions of four structurally related flavonoids (quercetin, kaempferol, rutin and luteolin) with Cu2+ ions were investigated in terms of the extent to which they undergo complex formation through chelation or modification through oxidation, as well as in their structural dependence. The ortho 3ʹ,4ʹ-dihydroxy substitution in the B ring is shown to be important for Cu2+-chelate formation, thereby influencing the antioxidant activity. The presence of a 3-hydroxy group in the flavonoid structure enhances the oxidation of quercetin and kaempferol, whereas luteolin and rutin, each lacking the 3-hydroxy group, do not oxidize as readily in the presence of Cu2+ ions. The results also demonstrate that the reactivities of the flavonoids in protecting low-density lipoprotein (LDL) against Cu2+ ion-induced oxidation are dependent on their structural properties in terms of the response of the particular flavonoid to Cu2+ ions, whether chelation or oxidation, their partitioning abilities between the aqueous compartment and the lipophilic environment within the LDL particle, and their hydrogen-donating antioxidant properties.