Objective:To investigate the clinical significance and possible mechanisms of elevated homocysteine(Hcy) levels in peripheral blood of children with sepsis.Methods:The clinical data of 51 children with sepsis (sepsis group) admitted to PICU at Xuzhou Children′s Hospital from January 2019 to December 2019 were analyzed, and the levels of Hcy in plasma were compared with 50 non-septic children (common infection group) and 50 healthy children (healthy control group) during the same period.The possible mechanism of metabolic disorders about Hcy was analyzed by detecting the levels of the key rate-limiting enzymes cystathionine-β-synthase(CBS) and cystathionine-γ-lyase(CSE), which were in the downstream of metabolism in septic mouse model induced by lipopolysaccharide.Results:The level of Hcy in plasma was (12.62±5.46)μmol/L in sepsis group, which was significantly higher than those in common infection group[(9.42±2.28) μmol/L] and healthy control group[(8.14±1.60) μmol/L]( P<0.05). The level of Hcy in plasma of 12 children with acute kidney injury in sepsis group was significantly higher than that of 39 children without acute kidney injury in sepsis group[(16.48±5.87)μmol/L vs.(11.62±4.74) μmol/L, P<0.05]. The level of Hcy in plasma of six children with acute liver failure in sepsis group was significant higher than that of 45 children without acute liver failure in sepsis group[(18.35±7.10) μmol/L vs.(11.84±4.78) μmol/L, P<0.05]. The level of Hcy in serum significantly increased in septic mouse models ( P<0.01). The transcription and protein expression levels of key rate-limiting Hcy transcription enzymes CBS and CSE in liver and kidney tissues of septic mouse were significantly down-regulated ( P<0.05). Conclusion:The level of Hcy in peripheral blood of children with sepsis increases, which is more obviously in children with acute kidney injury or acute liver injury.When patients developed sepsis, the expression of CBS and CSE will be restrained, leading to disorders related to transsulfuration metabolism and elevated level of Hcy in peripheral blood.