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Anemia is a global public health problem, especially common among children in developing countries, which affects their physical and mental health development. However, there is currently a lack of research on the relationship between anemia and academic performance. The objective of this study was to explore the association between anemia and academic performance, and the possible factors mediating this association among Chinese children. The data for this study came from the baseline survey of the Chinese Education Panel Survey Elementary School Cohort. The cohort was conducted from September 2018 to June 2019 in 160 elementary schools, covering 20 provinces and 40 counties/districts throughout China. Paper-based questionnaires were used, completed by 4th grade students, parents, head teachers, main teachers, and principals. The data used included questionnaire responses, physical measurements, and academic performance of 17,695 students. Based on students' hemoglobin levels and school altitude data, we grouped them into anemia and nonanemia categories using WHO criteria. The anemia group had 1,154 individuals, while the nonanemia group had 16,541 individuals. An ordinary least squares regression and mediation effect analysis were conducted. Our findings found the prevalence of anemia was 6.52% among Chinese Grade 4 students. Students without anemia had a higher average test score for three academic subjects than students with anemia (P < 0.001); their test scores for Chinese, Mathematics, and English were also higher (P < 0.05). Multivariate regression analysis showed a negative association between anemia and average test scores as well as individual test scores for the three subjects. Mediation analysis found that anemia affected academic performance directly (P < 0.05), and indirectly by decreasing the cognition score (P < 0.05). The indirect effect was 19.9% of the total effect. Findings highlighted anemia affected academic performance both directly and indirectly. Nutrition-related interventions should be implemented to prevent a decrease in academic performance among students with anemia. [ABSTRACT FROM AUTHOR]