Background: The current understanding of the immune landscape among the population following the widespread infection of SARS-CoV-2 in China by the end of 2022 is limited. The objective of this study was to evaluate the neutralizing activity of SARS-CoV-2 mutants (particularly JN.1) within the Chinese background and speculate on the future trajectory of the epidemic in China. Methods: Serum samples were collected from 340 people in Guangdong province at different time points between January 2023 and January 2024, and from 99 people who received three doses of inactivated virus vaccine before the outbreak. The pseudovirus neutralization assay was employed to investigate the neutralizing activities exhibited by these samples against three SARS-CoV-2 mutants. Results: Firstly, the low level of neutralizing antibody against BA.5 subbranches before the pandemic may be the cause of the national pandemic at the end of 2022. And the large-scale breakthrough infection increased the population’s immune resistance to BA.5, XBB.1.5/1.9.1, JN.1, thereby inhibiting the new wave of large-scale infection caused by XBB subbranches in China. Secondly, JN.1 had enhanced immune evasion capabilities. However, the levels of neutralizing antibodies against JN.1 in Chinese residents are comparable to those observed against XBB 1.5 among confirmed cases at the end of 2022. Conclusions: JN.1 will replace XBB subbranches as the predominant epidemic mutant in subsequent transmissions within China. However, it will be unlikely to cause a large-scale spread comparable to that witnessed at the end of 2022, with transmission patterns potentially resembling those observed for XBB post-pandemic.