Background: Sepsis is a serious condition, miR-34a is a microRNA (miRNA) that plays a critical role in the onset of inflammatory and autoimmune diseases. Single nucleotide polymorphisms (SNPs) in miRNA-coding genes have the potential to change miRNA function by influencing expression rates and target specificity, implicating them in disease. We conducted a case-control study to determine whether the two miR-34a SNPs (rs2666433 and rs6577555) polymorphism increase the risk of adult sepsis and affect the outcome of patients with adult sepsis in the Egyptian population. Methods: 70 critically ill adult septic patients who met the SOFA score criteria for clinical sepsis or septic shock and 70 adult normal controls were enrolled in the study, laboratory tests for sepsis for cases and control were done. Two miR-34a SNPs (rs2666433 & rs6577555) were chosen for analysis and correlated with sepsis parameters. Results: The rs6577555 SNP (CC and AC genotypes) and the rs2666433 SNP (GG genotype) were significantly higher in adult sepsis patients than the control. Univariate and Multivariate regression analysis revealed that the rs6577555 genotypes AC+CC, and WBC corelated with susceptibility to adult sepsis, while rs2666433 genotypes GG correlate with adult sepsis only by Univariate regression analysis. The relationship between the demographic data, laboratory investigations for adult sepsis patients and SNP were significant between rs6577555 (CC, AC) genotype and CRP, total serum bilirubin, while insignificant for rs2666433 genotypes. Conclusion: miR-34a polymorphism may be a useful indicator of adult sepsis and may provide a new direction for its treatment.