The aim of this study was to describe the clinical features, management strategies and outcomes of 31 infants with systemic capillary leak syndrome (SCLS) secondary to sepsis or systemic inflammatory response syndrome. There were 23 boys and 8 girls, with an average age 9.6 ± 2.1 days (range, 3.1 to 20 days). The primary disease was pneumonia in 11 patients and sepsis in other 20. Within 72 hrs of admission, all had progressive skin and mucosal edema, septic shock, respiratory distress, oliguria and severe hypoalbuminemia (10–20g/L). Other complications were pulmonary edema or hemorrhage, disseminated intravascular coagulopathy, heart failure, renal or liver dysfunction. All patients were treated with mechanical ventilation with a mean mechanical ventilation time of 19.7± 3.5 days. Intravenous hydroxyethyl starch was also applied at an early stage for 4–12 days, together with broad spectrum antibiotics, plasma and albumin infusion. Twenty one patients (67.0%) were discharged from the neonatal intensive care unit after a median stay of 29 days, and 7 died (37.0%) in the hospital. During a 6.3-month follow-up, 4 patients had hydrocephalus and another 4 had muscle spasm or rigidity in the lower-limbs. We conclude that SCLS is a serious complication of neonatal sepsis with a high rate of in-hospital mortality and post-discharge disability.