Brucellosis remains a major zoonosis worldwide; therefore, better understanding of its immunology is a priority for the development of new therapeutic and vaccination strategies. Genetic factors appear to have an important role in the pathogenesis of infectious diseases such as brucellosis. Adhesion molecules, such as members of the selectin family, participate in the interaction between leukocytes and the endothelium, as well as in inflammatory cell recruitment. The impact of L-selectin polymorphisms on brucellosis has not so far been investigated. The aim of this study was to assess an L-selectin Phe206Leu (F206L) polymorphism in patients with active brucellosis, and to analyse its possible relationship with disease progression. A case-control association study was carried out on 619 subjects, including 374 patients with brucellosis and 245 age- and sex-matched healthy controls. Genomic DNA was isolated, and amplification of L-selectin genomic regions was performed by PCR incorporating sequence-specific primers (PCR-SSP) to distinguish the genotypes. The frequencies of the F206L polymorphism were studied. A significant difference in F206L polymorphism was found between patients with brucellosis and controls. The 206Leu allele was more frequent in patients than in healthy individuals (36·6 versus 28 %, P=0·003). In addition, there was an association between the presence of the 206Leu allele and a relapse of brucellosis (odds ratio 6·53, 95 % confidence interval 1·5–28·8, P=0·005). The higher frequency of L-selectin genotypes in patients with brucellosis than in control individuals, as well as the association between the 206Leu allele and the occurrence of brucellosis relapse, suggest that the F206L polymorphism could make individuals more vulnerable to brucellosis.