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Objectives: This study aims to evaluate the association among framed messages (egoism-, altruism-, and loss-framed information), perceived net benefits (PNB), and willingness to receive a COVID-19 vaccine.Methods: A between-subject survey experiment was designed to assess the above association. A total of 1,316 individuals were included in this study. The participants were randomly assigned to one control group (receiving non-framed information) and three experimental groups (receiving egoism-, altruism-, and loss-framed information). The participants then reported their vaccination willingness and perceived effectiveness and side effects of vaccination. PNB was determined by subtracting the perceived side effects from perceived effectiveness.Results: Compared with the control group, participants in the experimental groups exhibited stronger vaccination willingness. Higher PNB levels were associated with enhanced vaccination willingness. However, only loss-framed messages indirectly affected vaccination willingness through PNB.Conclusion: PNB can mediate the impact of message framing on vaccination willingness. However, the mediation effect of PNB was only found in the relationship between loss-framed messages and vaccination willingness.