Preeclampsia (PE) occurs in 2–8% of pregnancies. It is one of the leading causes of maternal and perinatal morbidity and mortality. Today, there are no tests adopted by the practitioners that enable accurate prediction of early (weeks 20 through 34) or late (after week 34) onset of PE when the pregnancy is in its 11th to 14th week. This study aimed to evaluate the feasibility of using secretory clusterin quantification to predict early or late PE during the first trimester of pregnancy. The choice of this protein is determined, on the one hand, by the specificity of its expression for cytotrophoblast, syncytiotrophoblast, and extracellular trophoblast cells, and, on the other hand, by the proven negative effect of clusterin on the invasive properties of trophoblastic cells and gestational transformations of uterine vessels, which play a key role in the pathogenesis of PE. The study included 40 pregnant women aged 27–40 years who underwent a comprehensive screening examination in the first trimester of pregnancy. Western blotting revealed a significant increase in the level of secretory clusterin (40 kDa) in the blood serum of pregnant women in the case of PE compared to physiological pregnancy: in early-onset PE, a twofold increase in the level of clusterin in the vesicular and extravesicular fractions of blood serum (p = 0.03 and p = 0.004, respectively), with late-onset PE — a threefold increase only in the extravesicular fraction of blood serum (p = 0.002). According to logistic regression models, the level of secretory clusterin in the extravesicular fraction of blood serum of pregnant women in the first trimester has prognostic significance in assessing the likelihood of developing early-onset PE (AUC = 0.97, Se = 1, Sp = 0.875, cutoff = 0.3877) and late-onset PE ( AUC = 1, Se = 1, Sp = 1, cutoff = 0.5).