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This study investigated the mediating role of peer relatedness in the relationship between motivation and engagement in interprofessional education (IPE) among 841 students from various health professions in Hong Kong. Intrinsic motivation at baseline was found to increase engagement and reduce disaffection four weeks later, while extrinsic motivation showed the opposite effect. Notably, the link between motivation and engagement/disaffection in IPE was partially explained by students’ relatedness within IPE teams. The findings emphasize the importance of peer relatedness in harnessing student motivation and fostering engagement in IPE, contributing to a deeper understanding of the psychosocial mechanisms in IPE and highlighting the value of collaborative learning environments in fulfilling students’ need for relatedness and promoting adaptive IPE learning outcomes.