A comparative analysis between soluble (s) P-selectin and von Willebrand Factor (vWF) was performed in 40 patients with chronic obstructive pulmonary disease (COPD) and 20 healthy subjects, with the aim of investigating whether the occurrence of elevated levels of sP-selectin may reflect activation of platelets, endothelial cells, or both. Plasma sP-selectin levels were significantly higher in patients compared to controls (P < 0.01). Similarly vWF levels were elevated in patients compared to healthy subjects, although the difference did not reach statistical significance. Lipoprotein (a) [Lp(a)] levels were lower in COPD patients than controls (P < 0.0001). The analysis of the correlation among all the variables demonstrated that plasma sP-selectin did not correlate with vWE. Conversely, plasma sP-selectin levels significantly correlated with either oxygen (rho = -0.41, P < 0.05) or carbon dioxide (rho = 0.47, P < 0.05) tension. An inverse correlation between serum Lp(a) and plasma sP-selectin levels (rho = -0.35, P < 0.05) was also observed. Moreover, increasing levels of sP-selectin in COPD patients significantly correlated with the impairment of blood gas tensions. In conclusion, the results obtained indicate the prominent platelet origin of circulating sP-selectin, suggesting that sP-selectin might be considered a marker of in vivo platelet activation in patients with COPD.