OBJECTIVE: To determine the influence of meningococcal sepsis on levels of platelet derived CD40L and on endothelial CD40 expression. DESIGN AND SETTING: Prospective observational study in two tertiary paediatric intensive care units. PATIENTS AND PARTICIPANTS: 63 children with meningococcal sepsis and 10 age-matched controls. MEASUREMENTS AND RESULTS: (a) sCD40L ELISA of plasma from patients with meningococcal sepsis (n = 49) and age matched controls (n = 10). This demonstrated higher sCD40L levels in patients (median 0.29 ng/ml, IQR 0.2-0.41) than controls (0.09 ng/ml, 0.08-0.12). However, there was no relationship between plasma sCD40L level and platelet count or disease severity. (b) Flow cytometry of fresh blood from patients with meningococcal sepsis (n = 11) and age-matched controls (n = 10) for membrane bound CD40L and CD62P on circulating platelets. This demonstrated low levels of CD40L and CD62P in patients and controls. CD40L+ platelets were 3.5% (3.0-4.8) in patients and 4.9% (3.5-4.3) in controls. CD62P+ platelets were 10.7% (6.4-12.8) in patients and 7.9% (5.9-13.0) in controls. (c) Immunohistochemistry of skin biopsy specimens from six patients, staining for endothelial CD40 expression at sites of microthrombus formation, which demonstrated preserved CD40 expression in vascular endothelium at sites of microthrombus formation. CONCLUSIONS: The elevated sCD40L level in meningococcal sepsis implies release of sCD40L from platelets. However, there was no relationship between plasma sCD40L level and the degree of thrombocytopenia or disease severity. Furthermore, platelet surface bound CD40L was similar in controls and patients. Thus, further investigation is needed to determine whether platelet CD40L contributes to inflammation and thrombosis in MCS.