The balance between maternal immune responses and tolerance is considered as especially critical issue in the dilemma of recurrent pregnancy loss (RPL). Interleukin 6 (IL6) plays a fundamental role in fetal implantation and maintenance of pregnancy. This study aimed to explore the association between IL6–634 G/C gene polymorphisms and their serum levels in females with RPL. An observational case-control study involved 102 controls and 102 cases with RPL. Genotyping of IL6 polymorphism − 634 G/C was done with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and their serum levels were measured. There was no statistically significant difference between controls and RPL cases as regard serum IL6 level. The percentage of distribution for allele G was 88.7%, and 78% in controls and cases respectively (p = 0.005). The risk of RPL was decreased by 60% in carriers of allele G (OR = 0.4, 95%CI: 0.2–0.8, p = 0.003). Besides, the homozygote genotype GG (OR = 0.5, 95%CI: 0.28–0.95, p = 0.031), was linked with decreased risk for RPL. The homozygous GG genotype and G allele were associated with decreased risk of RPL in Egyptian females