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This study examined the relationship between the domain-based epistemological beliefs and the components of course motivation for first-year undergraduate students in biochemistry using cluster analysis and MANOVA. A two-step cluster analysis led to five student profiles based on responses to a survey of students’ epistemological beliefs related to biochemistry. The five profiles showed groups of students who hold distinctly different beliefs about knowledge in biochemistry. The MANOVA and post-hoc tests comparing students’ course motivation using the MUSIC model of academic motivation showed no statistically significant differences amongst components of the groups’ course motivation. Preliminary coding of open-ended questions suggests that the EB profiles describe different types of course activities as autonomy-supportive, useful, and supporting their success in biochemistry.