Variation at the porcine DECR1 and ME1 genes has been associated with meat quality traits and backfat thickness in Landrace pigs, respectively. However, it has not been investigated yet whether DECR1 and ME1 genotypes influence lipid composition. With this aim, we have genotyped two missense DECR1 substitutions (c.160G>C and c.437G>C) and one silent ME1 (c.576C>T) polymorphism in 361 Duroc barrows distributed in five half-sib families and phenotyped for serum lipid concentrations and intramuscular fat content and composition traits. At the whole-population level, relevant associations, that is, with a posterior probability of the allele substitution effect to be over or below zero (PPN0) > 0.90, were observed between DECR1 genotype and serum cholesterol (CHOL) (PPN0 = 0.932) and LDL concentrations (PPN0 = 0.945) at 190 days, as well as between ME1 genotype and longissimus dorsi saturated fatty acid content (PPN0 = 0.924). At the within-family level, we found relevant associations between DECR1 and ME1 genotypes and diverse lipid composition traits, but most of them were family-specific. Discrepancies in allele substitution effects estimated in half-sib families might be produced by many factors such as number of individuals, marker allele frequencies and informativeness in each family, unaccounted random genetic and environmental effects, epistasis and family-specific differences in the linkage phase or amount of linkage disequilibrium between causal and marker mutations. This lack of consistency across families, combined with the fact that the ME1 mutation is synonymous and that the two DECR1 polymorphisms are conservative, suggests that the associations found are not causative.