BackgroundSystemic low‐grade inflammation has been proposed as an underlying pathophysiological mechanism for cardiometabolic diseases. We investigated the associations of physical fitness with a systemic low‐grade inflammatory state in a population sample of children.MethodsAltogether 391 children aged 6–9 years were examined. Cardiorespiratory fitness (maximal power output, W_max) was assessed by a maximal cycle ergometer test and neuromuscular fitness by hand grip strength, sit‐up, standing long jump, 50‐meter shuttle run, static balance, sit‐and‐reach, and box and block tests. Body fat percentage (BF%) and lean mass (LM) were assessed by dual‐energy X‐ray absorptiometry (DXA). High sensitivity C‐reactive protein (hs‐CRP), leptin, leptin receptor, high molecular weight adiponectin (HMW‐adiponectin), interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), and glycoprotein acetyls (GlycA) were assessed from fasting blood samples. The modified inflammatory score (IS) was calculated using the population‐specific z‐scores and formula (^zhs‐CRP + ^zleptin + ^zIL‐6 + ^zTNF‐α + ^zGlycA)—^zleptin receptor—^zHMW‐adiponectin. The data were analyzed using linear regression analyses.ResultsHigher W_max/kg of body mass (β = −0.416, 95% CI = −0.514 to −0.318), higher number of completed sit‐ups (β = −0.147, 95% CI = −0.244 to −0.049), a longer distance jumped in the standing long jump test (β = −0.270, 95% CI = −0.371 to −0.169), and a shorter time in the 50‐meter shuttle run test (β = 0.123, 95% CI = 0.022 to 0.223) were associated with lower IS. None of these associations remained statistically significant after adjustment for BF%.ConclusionsHigher physical fitness is associated with a more favorable inflammatory biomarker profile in children. However, the associations were explained by BF%.