Lithium–oxygen batteries promise high energy but suffer from poor cycle life owing to the generation of highly reactive singlet oxygen ¹O₂, which rapidly deactivates the electrode and the electrolyte. Here we demonstrate an effective strategy to suppress ¹O₂ using redox mediators. Using operando spectroscopy techniques, we show that 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), as a model redox mediator, drastically reduces ¹O₂ formation, increases the yield of ground state ³O₂, and reduces the by-product generation. The ¹O₂ suppression effect is attributed to an increased intersystem crossing rate induced by redox mediators, with which the relaxation of a singlet-state intermediate to a triplet-state one is accelerated. We further show that this ¹O₂ suppression effect applies universally across six common redox mediators with up to three orders of magnitude higher ¹O₂ suppression efficiency compared to 1,4-diazabicyclo[2.2.2]octane (DABCO), the most efficient quencher used in Li–O₂ batteries to date. From the comparison of the investigated mediators we discuss the plausible governing principle dictating redox mediators’ effectiveness in suppressing ¹O₂. Our study achieves effective ¹O₂ suppression and provides guidelines for designing redox mediators for efficient and reversible lithium–oxygen batteries.