Scope: This study examined to what extent plasma linoleic acid (LA) is modified by adiposity, and explored any association between plasma LA, demographics, dietary intakes, markers of metabolic health and haplotypes of the fatty acid desaturase (FADS) 1/2 genes. Methods and results: 820 participants with fasting blood samples from Irish National Adult Nutrition Survey were studied. Plasma fatty acids were determined using GC-MS. 15 SNPs of FADS 1/2 genes were genotyped. Plasma LA decreased while γ-linoleic acid and dihomo-γ-linoleic acid increased in overweight/obese participants (P ≤ 0.002). Participants in the highest quartile of plasma LA showed decreased plasma markers of de novo lipogenesis, insulin resistance and of inflammation (TNF-α, PAI-1) (P ≤ 0.005). Adiposity (waist circumference and body fat) was strongly inversely associated with plasma LA accounting for 11.8% of variance observed, which was followed by FADS1/2 haplotypes (3.9 %), quantity and quality of carbohydrate intakes (3.8 %), dietary PUFA intakes (3.7 %), systolic blood pressure (3.6 %) and age (3.2 %). Conclusion: Plasma LA was inversely associated with adiposity, followed by haplotypes of FADS1/2 genes, carbohydrate intakes and dietary PUFA intakes. The association observed between plasma LA and adiposity may be linked to decreased de novo lipogenesis, insulin resistance and inflammation.