Leptin is a hormone produced by adipocytes, and its expression is regulated by body fatness and energy balance. This study describes the association of four leptin gene polymorphisms in dairy cows (R4C, A59V, RFLP1, and BM1500) with circulating leptin concentrations during the periparturient period. A59V is located at a between-species conserved region of leptin, and R4C might have effect on the tertiary structure of the leptin protein because of the presence of an extra cystein. RFLP1 is an intronic SNP and BM1500 is a microsatellite located 3.6 kb downstream of the leptin locus. The four polymorphisms were genotyped in 323 HF heifers with known pedigree. Leptin concentrations were determined biweekly from 30 days before until 80 days after parturition. The effect of genotype on leptin concentrations was modeled by fitting a spline in ASREML describing leptin concentrations as a function of days relative to parturition for each genotype/allele. Surprisingly, associations were found during pregnancy, but not during lactation. This indicates that the polymorphism could be more effective during pregnancy. If further studies demonstrate that more leptin-binding protein (Ob-Re) is present in this stage, it is hypothesized that a structural difference in the leptin protein could cause a sub-optimal binding stringency to Ob-Re. Free leptin could be cleared faster than bound leptin, and this could result in lower leptin concentrations during pregnancy for the polymorphism. The effects found might be ascribed to R4C. However, more study on the Ob-Re receptor, like binding stringencies between R4C and wild-type leptin and glycosylation during pregnancy, would provide more insight in the results found.