Background Among the adaptive capacities of animals, the management of energetic body reserves (BR) through the BR mobilization and accretion processes (BR dynamics, BRD) has become an increasingly valuable attribute for livestock sustainability, allowing animals to cope with more variable environments. BRD has previously been reported to be heritable in ruminants. In the present work, we conducted genome-wide studies (GWAS) in sheep to determine genetic variants associated with BRD. BR (i.e. levels) and BRD (i.e. changes over time) were obtained through body condition score measurements at eight physiological stages throughout each productive cycle in Romane ewes ( n = 1034) and were used as phenotypes for GWAS. After quality controls and imputation, 48,593 single nucleotide polymorphisms (SNP) were included in the GWAS. Results Among the 23 QTL regions identified, a major QTL associated with BR during pregnancy and lactation was identified on chromosome 1. In this region, several significant SNPs mapped to the leptin receptor gene (LEPR), among which one SNP mapped to the coding sequence. The point mutation induces the p.P1019S substitution in the cytoplasmic domain, close to tyrosine phosphorylation sites. The frequency of the SNP associated with increased BR levels was 32%, and the LEPR genotype explained up to 5% of the variance of the trait. Higher fatness levels in ewes carrying the LEPR p.P1019S mutation were observed all along the productive cycle. Conclusions These results provide strong evidences for involvement of LEPR in the regulation of BR in sheep and highlight it as a major candidate gene for improving adaptive capacities by genetic selection.