Abstract: Although it first appeared almost two years ago, the COVID-19 pandemic continues to have an impact on a global scale, in part due to newly emerging SARS-CoV-2 variants such as Delta and Lambda. The B.1.621 variant, first identified in Colombia in January 2021, was classified as a variant of interest (VOI) and designated as Mu by the World Health Organization (WHO) in August 2021. However, its infectivity and resistance to neutralizing antibodies remain largely unknown. Here, in comparison to Delta, the Mu variant showed an unexpectedly enhanced immune resistance to inactivated vaccine-elicited antibodies. Nevertheless, Mu demonstrated less infectivity than Delta, implying a biological trade-off between viral transmission and immune escape. This study strongly calls for urgent evaluation of the protective efficacy of current COVID-19 vaccines against the Mu variant.