Objective To investigate soluble P-selectin (sP-selectin) levels and platelet parameters in normal pregnant women compared with non-pregnant control subjects. Design A longitudinal case -control study.Setting Obstetric outpatient clinic in the Jubilee Maternity Hospital, Belfast.Population One hundred and twenty normal pregnant women and 41 non-pregnant age-matched control subjects. Methods The plasma concentration of sP-selectin in pregnant women sampled at 12, 20 and 35 weeks of gestation, and, in a subgroup at three days postpartum, and non-pregnant controls sampled in parallel, was determined using a commercial quantitative sandwich immunoassay kit. Platelet parameters on each blood sample were also recorded using a SYSMEX SE 9500 analyser. Main outcome measures Plasma sP-selectin as a measure of platelet activation in normal pregnancy.Results Soluble P-selectin was significantly higher in pregnant women than in non-pregnant control subjects at 20 and 35 weeks of gestation, ( P < 0.01, and P < 0.001, respectively). Correlation analyses showed positive correlation between sP-selectin and platelet count in pregnant women at 20 and 35 weeks of gestation (r ¼ 0.247, P < 0.05 and r ¼ 0.360, P < 0.001, respectively). Soluble P-selectin concentration per platelet was also significantly higher in pregnant women than in non-pregnant control subjects at 20 and 35 weeks of gestation ( P < 0.001). Conclusions Our results show that sP-selectin concentration is significantly higher in the second and third trimester of pregnancy when compared with non-pregnant control subjects sampled in parallel. This finding clarifies previous conflicting results on platelet activation in normal pregnancy, and is in agreement with those earlier studies which reported, using other methods, increased platelet activation in normal pregnancy.