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To examine the relationship between a battery of obesity indicators and physical fitness components with academic performance in children and to explore the combined and mediation role of the physical fitness components in the relationship between obesity and academic performance in children.A cross-sectional study including data from 250 Spanish schoolchildren (Balearic Islands) between 10 and 12 years of age (mean age, 10.98 ± 0.76 years) was conducted. Obesity measures (body mass index, body fat, waist circumference, hip circumference, and waist-to-height ratio), physical fitness components (cardiorespiratory fitness, muscular fitness, and speed-agility), and academic performance (Spanish language, Catalan language, English language, natural sciences, social sciences, arts, physical education, religion, and grade point average [GPA]) were collected.All obesity measures were negatively related to at least 3 of the 10 academic indicators, including GPA (β range, −0.135 to −0.229; all P < .05). Cardiorespiratory fitness and speed-agility were positively related to all academic indicators (β range, 0.182 to 0.350; all P < .046) and muscular fitness with 3 academic indicators (β range, 0.143 to 0.253; all P < .039). Children considered as fit had better academic performance than their unfit peers (score +0.75; P = .001). The association between body mass index and GPA was mediated by cardiorespiratory fitness and speed-agility.This investigation contributes to the current knowledge by adding evidence about the crucial role of physical fitness in terms of academic performance rather than obesity status, suggesting that physical fitness may ameliorate the negative influence of obesity on academic performance.