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The present study investigated the effects of an informal learning program, STEM behind Sickle Cell (SBSC), on students’ motivation for sickle cell disease related STEM (SCD-STEM) learning and STEM identity. There were three key instructional components in each topical module of the program—STEM knowledge related to sickle cell, scientific literacy and epistemology, and science communication, and students learned and developed their own SCD storytelling projects at the end of the program. As showed by the pretest-posttest comparisons, participants had significantly enhanced self-relevance, task value, inference-making ability, and STEM identity with considerable effect sizes. Data on student projects and coordinator interview also confirmed a strengthened sense of relevance, motivation, and interest for learning SCD-STEM in the program.