Polymorphisms (SNPs) within the FADS gene cluster and the ELOVL gene family are believed to influence enzyme activities after an omega-3 (n-3) fatty acid (FA) supplementation. The objectives of the study are to test whether an n-3 supplementation is associated with indexes of desaturase and elongase activities in addition to verify whether SNPs in the FADS gene cluster and the ELOVL gene family modulate enzyme activities of desaturases and elongases. A total 208 subjects completed a 6-week sup-plementation period with 5 g/day of fish oil (1.9–2.2 g/day of EPA ? 1.1 g/day of DHA). FA profiles of plasma phospholipids were obtained by gas chromatography (n = 210). Desaturase and elongase indexes were estimated using product-to-precursor ratios. Twenty-eight SNPs from FADS1, FADS2, FADS3, ELOVL2 and ELOVL5 were genotyped using TaqMan technology. Desaturase indexes were significantly different after the 6-week n-3 supple-mentation. The index of d-5 desaturase activity increased by 25.7 ± 28.8 % (p \ 0.0001), whereas the index of d-6 desaturase activity decreased by 17.7 ± 18.2 % (p \ 0.0001) post-supplementation. Index of elongase activity decreased by 39.5 ± 27.9 % (p \ 0.0001). Some gene–diet interactions potentially modulating the enzyme activities of desaturases and elongases involved in the FA metabolism post-supplementation were found. SNPs within the FADS gene cluster and the ELOVL gene family may play an important role in the enzyme activity of desaturases and elongases, suggesting that an n-3 FAs supplementation may affect PUFA metabolism. Keywords Omega-3 fatty acids Á Diet and dietary lipids Á Genomics Á Fish oil Á Omega-6 fatty acids Á Genotype