Aim To explore the serum soluble cell differentiation antigen 40 ligand (sCD40L) level and its significance in patients with acute cerebral infarction. Methods Serum sCD40L level was measured by two-layer antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 62 patients with acute cerebral infarction and 30 healthy controls matched in sex and age. Results Serum sCD40L level was significantly higher in patients with acute cerebral infarction than that in control [(2.32±1. 29) μg/L vs (0.68±0.56) μg/L,p<0.01]. Serum sCD40L level in patients with acute cerebral infarction was positively related to apolipoprotein B₁₀₀ (ApoB₁₀₀) (r=0.267, p<0.05) and triglyceride (TG) (r=0.254,p<0.05) and negatively related to high density lipoprotein cholesterol (HDLC) (r=-0.272,p<0.05). Conclusions The sCD40L level was significantly elevated in acute cerebral infarction patients within 72 h of onset, which may be related to the pathogenesis of acute cerebral infarction.