Removing mercury in wet natural gas containing acidic components is essential to developing the natural gas purification industry and mitigating corrosion in aluminum heat exchangers. In this work, the Cu-doped manganese oxide octahedral molecular sieve (OMS-2) nanorods were designed for oxidation of Hg0 in wet natural gas. The Hg0 removal efficiency over Cu(0.05)-OMS-2 reached 98.2 % under a high space velocity of 24 × 104 h−1 and a complex atmosphere containing H2O, CO2, and H2S. Surface reactive oxygen species produced by strong electronic interactions owing to Mn-O-Cu hybridization was the main active sites for Hg0 oxidation. The reactive oxygen species on Cu(0.05)-OMS-2 reacted with H2S to form active sulfur species, which could combine with Hg0 to form HgS. Cu(0.05)-OMS-2 exhibited excellent ambient-temperature water resistance, which was attributed to the good redox properties caused by Cu incorporation. This work provided a new strategy for designing efficient sorbents to remove Hg0 from wet natural gas.