To better understand the early development of cardiovascular disease, we examined the association of adiposity measures and cardiorespiratory fitness (CRF) with baseline values and changes in low-grade chronic inflammation and insulin resistance (IR) in school children. Eighty-three 1(st) and 5(th) grade children from a randomly selected control group of a physical activity intervention study (KISS) were prospectively studied during one academic year. Outcome variables included highly sensitive C-reactive protein (hs-CRP) and homeostasis assessment of IR (HOMA-IR). Adiposity measures included body mass index (BMI), waist circumference and the sum of skinfold thickness at four sites. CRF was assessed by the 20 m shuttle run test. All models were adjusted for age group, sex and pubertal group and included children who had a complete valid dataset for all variables. Baseline metabolic markers correlated positively with measures of adiposity and inversely with CRF (all p ≤ 0.02). On average, longitudinal changes in hs-CRP concentration increased with high baseline BMI in boys and skinfold thickness in both genders (both p < 0.01). Increases in adiposity had an additional effect on these changes (adjusted R(2) of the models including baseline and change in adiposity 0.49-0.53, p < 0.001). On the other hand, longitudinal changes in HOMA-IR were positively related to changes in BMI and waist circumference (p ≤ 0.03). Increases in HOMA-IR, but not in hs-CRP concentrations, were associated with low baseline CRF (p = 0.01). The relationship of baseline adiposity and CRF with increases in metabolic risk markers may have relevant implications for long-term cardiovascular risk. International Standard Randomised Controlled Trial Number (ISRCTN): isrctn.org 15360785.