Previous studies suggested a strong genetic effect on the sepsis pathogenesis. This research aimed to assess role of miRNA-146-a expression in pediatric sepsis. Methods: Our study included 55 pediatric sepsis patients and 60 control children of the same age and sex. Serum miRNA-146-a expression was measured using quantitative real time polymerase chain reaction. C-reactive protein, interleukin-6, tumor necrosis factor-α, procalcitonin levels were measured by ELISA. The outcome of the pediatric sepsis group was determined at 28 days follow up period. Results: Our results revealed that serum miRNA-146-a levels were significantly decreased in sepsis group in comparison to control group. Serum level of miRNA-146a correlated with sepsis severity where pediatric septic shock group having lowest level followed by severe sepsis and sepsis groups. miRNA-146-a level could diagnose sepsis (area under curve (AUC) = 0.803). Serum miRNA-146-a expression was negatively associated with CRP, pro-calcitonin, IL-6 and TNF-α. Patients with miRNA-146-a level lower than 0.4 had increased mortality rate. Conclusions: miRNA-146-a is of significant diagnostic and prognostic value in pediatric sepsis and could be used for planning therapeutic strategies