Background: Sepsis is a leading cause of pediatric morbidity and mortality worldwide. The aim of this study was to explore the association of decreased mitochondrial respiratory chain enzyme activities with the risk for pediatric sepsis, and explore their association with mortality among affected children. Methods: A total of 50 incident cases with sepsis and 49 healthy controls participated in this study. The level of serum coenzyme Q10 was measured by high-performance liquid chromatography, and selected mitochondrial respiratory chain enzymes in WBC were measured using spectrophotometric. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI). Results: The levels of CoQ10, complex II, complex I + III and FoF1-ATPase were significantly higher in healthy controls than in children with sepsis (p<0.001,= 0.004, < 0.001 and <0.001, respectively). In children with sepsis, levels of CoQ10 and complex I +III were significantly higher in survived cases than in deceased cases (p < 0.001). Per 0.05 mu mol/L, 50 nmol/min.mg and 100 nmol/min.mg increment in CoQ10, complex I + III and FoF1-ATPase were associated with significantly lowered risk of having sepsis, even after adjusting for confounding factors (OR= 0.85, 0.68 and 0.04, p= 0.001, < 0.001 and <0.001, respectively). Per 0.05 mu mol/L and 50 nmol/min.mg increment in CoQ10 and complex I + III was associated with significantly lowered risk of dying from sepsis during hospitalization, and significance retained after adjustment (OR= 0.73 and 0.76, 95% CI: 0.59 to 0.90 and 0.64 to 0.89, p= 0.004 and 0.001, respectively) in children with sepsis. Conclusions: Our findings indicate the promising predictive contribution of low serum CoQ10 and complex I + III to the risk of pediatric sepsis and its associated mortality during hospitalization among Chinese children.