The cryo-EM data were collected at the Shanghai Advanced Electron Microscope Center. Funding: This work was partially supported by Ministry of Science and Technology (China) grants (2018YFA0507002 to H.E.X.); Shanghai Municipal Science and Technology Major Project (2019SHZDZX02 to H.E.X.); Shanghai Municipal Science and Technology Major Project (H.E.X.); CAS Strategic Priority Research Program (XDB37030103 to H.E.X.), National Natural Science Foundation of China (32130022 to H.E.X.); the Youth Innovation Promotion Association of CAS (2021278 to W.Y.), National Natural Science Foundation of China (32171189 to W.Y.), National Science Fund for Excellent Young Scholars (82122067 to W.Y.), Key tasks of LG laboratory (LG202103-03-05 to W.Y.); Fund of Youth Innovation Promotion Association (2018319 Y8G7011009 to X.C.); Science and Technology Commission of Shanghai Municipal (20431900100 to H.J.) and Jack Ma Foundation (2020-CMKYGG-05 to H.J.); National Natural Science Foundation (31770796 to Y.J.) and National Science and Technology Major Project (2018ZX09711002 to Y.J.); National Natural Science Foundation of China (81902085 to Y.X.); Shanghai Municipal Science and Technology Major Project (to J. Z.). China Postdoctoral Science Foundation Funded Project (Project No.E11289R078 to C.W.); Key tasks of LG laboratory (LG202101- 01-03 to Y. X.). Author contributions: W.Y. designed the expression constructs, purified the Spike complex proteins, screened the cryo-EM conditions, prepared the cryo-EM grids and collected cryo-EM images toward the structures, and participated in figure and manuscript preparation. Y.X. collected cryo-EM images with the help of Q.Y., K.W. and W.H, performed density map calculations and participated in the model building and refined the final models with P.X., Y.X., P.X. and C.W. participated in figure and manuscript preparation. X.W. purified the ACE2 protein. S.H. performed the AlphaScreen assays. H.J. supervised X.C., Z.H. and X.H., analyzed the molecular 13 dynamics simulations and participated in figure preparation. J. Z. supervised B.S., detected the HDX data by mass spectrometry and participated in figure preparation; Y.J. participated in experimental design and manuscript editing. S. D. supervised X.C., C.G., J.L., Z.W., F.J., K.X., P.L., and X.W., provided the JMB2002 antibodies, performed the function assays for JMB2002 antibodies and spike proteins, and participated in manuscript writing; H.E.X. conceived and supervised the project, analyzed the structures, and wrote the manuscript with inputs from all authors. Competing interests: Wanchao Yin, Youwei Xu, Peiyu Xu, Canrong Wu, Xinheng He, Xiaoxi Wang, Sijie Huang, Qingning Yuan, Kai Wu, Wen Hu, Zifu Huang, Bin Song, Jie Zheng, Hualiang Jiang, Xi Cheng, Yi Jiang, H. Eric Xu have declared no competing interest. Xiaodan Cao, Chunyin Gu, Jia Liu, Zongda Wang, Fangfang Jia, Kaiwen Xia, Peipei Liu, Xueping Wang, and Su-Jun Deng are employee of Shanghai Jemincare Pharmaceuticals, and are developing JMB2002 as a potential anti-Omicron therapeutic. Data and materials availability: Density maps and structure coordinates have been deposited with immediate release. The accession numbers of Electron Microscopy Database and the Protein Data Bank are EMD-32679 and PDB ID 7WP9 for Omicron spike trimer; EMD-32680 and PDB ID 7WPA for Omicron spike trimer in complex with hACE2; EMD-32681 and PDB ID 7WPB for local refined reconstruction of Omicron spike RBD in complex with hACE2; EMD-32682 and PDB ID 7WPC for local refined reconstruction of a second Omicron spike RBD in complex with RBD-hACE2; EMD-32683 and PDB ID 7WPD for Omicron spike trimer in complex with one JMB2002 Fab; EMD-32684 and PDB ID 7WPE for Omicron spike trimer in complex with two JMB2002 Fab; EMD-32685 and PDB ID 7WPF for Omicron spike trimer in complex with three JMB2002 Fab, EMD-32736 and PDB ID 7WRV for local refined reconstruction of Omicron spike RBD in complex with JMB2002 Fab. Materials are available upon request. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.