The reactions of three iridium water-oxidation catalysts {[Cp*IrL¹L²L³]X_n; 1: L¹, L² = 2,2-bipyridine (bpy), L³ = Cl, n = 1, X = Cl; 2: L¹, L² = 2-benzoylpyridine (bzpy), L³ = NO₃; 3: L¹ = L² = L³ = H₂O, n = 2, X = NO₃; Cp* = pentamethylcyclopentadienyl} with cerium ammonium nitrate (CAN) and NaIO₄ (sacrificial oxidants, SOs) have been studied by Clark electrode measurements (both in solution and in the gas phase), on-line mass spectrometry, manometry and UV/Vis spectroscopy. Furthermore, cyclic voltammetry has been applied to evaluate the relative tendency of 1 and 2 to be oxidized. The turnover frequency (TOF) increases as the ratio (R) between the concentration of the SO and that of the catalyst increases. O₂ production with CAN is observed in experiments with R = 20 for 1 and 3, whereas O₂ becomes detectable with 2 only when R = 40. Catalyst 2 has the highest tendency to be oxidized to Ir^IV and forms a blue intermediate I characterized by a UV/Vis band at 574 nm. The formation of I occurs with the same velocity as that of the production of O₂, which indicates that I is a species directly involved in the catalytic cycle. The disappearance of I, when O₂ evolution is finished, is a second-order process more than one order of magnitude slower than O₂ production and is strongly accelerated by the presence of benzyl alcohol. This suggests that I is a molecular species that slowly undergoes disproportion when catalysis is over. Experiments in which multiple aliquots of SO (CAN) were added (R = 20 and 40) indicate that catalysts 1–3 can reinitiate the catalytic cycle once they have been kept in a dormant state for 0–9 min; the TOFs of the second and third additions are approximately equal and higher than that of the first addition. By combining manometry and on-line mass spectrometry measurements, it was found that O₂ evolution is parallel to the production of a small amount of CO₂ owing to catalyst degradation. The TOFs of the experiments performed with NaIO₄ as the SO are about 2–3 times lower than those with CAN, but the same reactivity order is found 3 > 2 > 1. The activation parameters were evaluated with NaIO₄ for all catalysts and with CAN for 2 at 10–45 °C. ΔG^# is practically the same in all situations (25–26 kcal mol^–1), whereas ΔH^# is appreciably lower for 2 (13.1 kcal mol^–1 with CAN and 13.3 kcal mol^–1 with NaIO₄) than for 1 (16 kcal mol^–1) and 3 (16.9 kcal mol^–1). The lowest enthalpic cost with 2 is balanced by the highest entropic cost (–41 cal mol^–1 K^–1) that approaches that typical for an associative bimolecular process.