BackgroundExcessive body weight has been related to lower cognitive performance. One of the mechanisms through which excess body weight may affect cognition is inflammation. HypothesisOur hypothesis is that both body mass index (BMI) and circulating levels of inflammatory biomarkers will be negatively related to cognitive performance. DesignCross-sectional study. SettingUsers of the public health centres of the Consorci Sanitari de Terrassa (Terrassa, Spain) between 2010 and 2017 aged 12–21 years. ParticipantsOne hundred and five adolescents (46 normoweight, 18 overweight, 41 obese). MeasurementsLevels of high sensitivity C-reactive protein, interleukin 6, tumour necrosis factor α (TNFα) and fibrinogen were determined from blood samples. Cognitive performance was evaluated and six cognitive composites were obtained: working memory, cognitive flexibility, inhibitory control, decision-making, verbal memory, and fine motor speed. A single multivariate general lineal model was used to assess the influence of the four inflammatory biomarkers, as well as participants’ BMI, sex, and age on the 6 cognitive indexes. ResultsAn inverse relationship between BMI and inhibitory control (F = 5.688, p = .019; β = −0.212, p = .031), verbal memory (F = 5.404, p = .022; β = −0.255, p = .009) and fine motor speed (F = 9.038, p = .003; β = −0.319, p = .001) was observed. Levels of TNFα and fibrinogen were inversely related to inhibitory control (F = 5.055, p = .027; β = −0.226, p = .021) and verbal memory (F = 4.732, p = .032; β = −0.274, p = .005), respectively. LimitationsThe cross-sectional nature of the study, the use of cognitive tests designed for clinical purposes, and the use of BMI as a proxy for adiposity are limitations of our study that must be taken into account when interpreting results. ConclusionsOur data indicate that some components of executive functions, together with verbal memory, are sensitive to specific obesity-related inflammatory agents at early ages.