This work describes the differential quenching of molecular oxygen and superoxide anion radical (O2˙–) by (metallo)‐quercetin (QCR) complexes. The in situ complexes were more reactive with molecular oxygen than preformed complexes. By adjusting the potential range, it was determined that Cu2+ complexes exhibited similar superoxide anion radical (O2˙–) quenching ability as free QCR. The Fe3+ complexes were less reactive than free QCR or Cu2+ complexes. The data indicate that metal ions significantly modulated reactivity of QCR with O2˙– or molecular oxygen, and may regulate antioxidant activity and reactive oxygen species levels in a complex biological setting.