The human leukocyte antigen G (HLA-G) is a molecule involved in immune system modulation, acting in the maintenance of a state of immune tolerance. Some polymorphisms in the HLA-G gene 3′ untranslated region (3′UTR) were associated to distinct levels of HLA-G expression and to sepsis development. In the present study, haplotypes and polymorphisms of the HLA-G 3′UTR were analyzed in Brazilian septic patients. The HLA-G 3′UTR was amplified by PCR, sequenced and eight polymorphisms were genotyped (the 14bp insertion/deletion, +3003T/C, +3010C/G, +3027A/C, +3035C/T, +3142G/C, +3187A/G and+3196C/G) in DNA samples from septic patients (with severe sepsis or septic shock) and controls. The haplotypes were inferred and association tests were performed through Chi square test and binary logistic regression. The+3027AC genotype was associated asa risk factor to sepsis development (OR 3.17, PBonferroni 0.048). Further, the presence of the UTR-7 haplotype (OR 2.97, PBonferroni 0.018), and of 14bp-Ins_+3142G_+3187A haplotype (OR 2.39, PBonferroni 0.045) were associated with sepsis, conferring susceptibility. Our data confirm an important role of HLA-G 3′UTR polymorphisms in the development of severe forms of sepsis (severe sepsis and septic shock). The genotyping of HLA-G genetic variants and haplotypes could be useful as a prediction tool of increased risk to severe sepsis.