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Assessing fatty acid (FA) composition in relation to inflammatory markers can shed light on the role of different FA and their metabolism in low-grade inflammation. Existing exploratory studies in children are scarce, and findings inconsistent. We hence aim to analyse associations of FA with common inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), in 10-year-old children.Complete data were available for 958 participants from the 10-year follow-up of the LISAplus (Influence of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus the Influence of Traffic Emissions and Genetics) birth cohort study. FA composition was assessed in serum glycerophospholipids. Hs-CRP and IL-6 were categorised into three levels. Associations of FA with inflammatory markers were assessed using multinomial logistic regression, adjusting for potential confounders. Additionally, sex-stratified analyses were carried out.FA exposures associated with significantly higher low-grade inflammation, as indicated by higher hs-CRP or IL-6 levels, included: palmitic acid (PA) (IL-6: P < 0.001, 95% confidence interval: 1.30; 2.43), arachidonic acid (AA) (hs-CRP: P = 0.002, 1.07; 1.31), n-6 highly unsaturated FA (HUFA) (hs-CRP: P = 0.002, 1.06; 1.27), ratio of AA to linoleic acid (AA/LA) (hs-CRP: P < 0.001, 1.16; 1.62) and total saturated FA (SFA) (IL-6: P < 0.001, 1.77; 3.15). FA exposures associated with reduced levels of inflammatory markers included LA (hs-CRP: P = 0.001, 0.84; 0.96; IL-6: P < 0.001, 0.69; 0.90) and total polyunsaturated FA (PUFA) (IL-6: P < 0.001, 0.57; 0.78).These findings suggest that higher SFA and minor n-6 HUFA, namely PA and AA, are associated with increased low-grade inflammation in children, whereas the major dietary n-6 PUFA and total PUFA are associated with reduced inflammation. Elevated desaturase activity, estimated by the ratio AA/LA, may be associated with higher inflammation, particularly in boys.