The cellular response to various types of stress underlying placental vascular dysfunction is under the sumoylation control. Consequently, SUMO homeostasis is closely related to the maintenance of angiogenic balance, the disruption of which is a feature of preeclampsia (PE). The goal of the research is to search for exosomal markers of such a disorder. The expression and prognostic potential of exosomal SUMO 1–4, UBC9 and hnRNPA2/B1 were evalueted in 39 pregnant women (cohort I) in the first trimester using Western blotting technology. The expression of these proteins in the placenta (cohort II, 27 pregnant women) at the time of delivery was also assessed. The expression of their conjugated forms was significantly changed in pregnant women with early-onset (SUMO 1, p = 0.03; SUMO 2/3/4, p = 0.03) and late-onset PE (SUMO 1, p = 0.03; SUMO 2/3/4, p = 0.04; UBC9 and hnRNPA2/B1, p < 0.0001, respectively). This change may be due to the functional specificity of SUMO isoforms in the context of their subcellular targets upon exposure to stressful stimuli. Significant changes in the expression of these proteins were also found in the placenta. Significant correlations were established between the expression of exosomal SUMO 2/3/4 (r = –0.59; p = 0.01) and UBC9 (r = –0.88; p = 0.0001) with PlGF in early-onset PE. In late-onset PE, hnRNPA2/B1 (r = –0.48; p = 0.03) and UBC9 (r = –0.48; p = 0.03) was correlated with β-hCG, and SUMO 2/3/4 with PAPP-A (r = –0.60; p = 0.006) in the blood serum of pregnant women. The analyzed proteins also significantly correlated with uterine artery pulsation index (SUMO 1 (r = 0.59; p = 0.01), SUMO 2/3/4 (r = 0.54; p = 0.02), hnRNPA2/B1 (r = 0.75; p = 0.0001)) and mean arterial pressure (UBC9 (r = 0.53; p = 0.03)). Based on the data the logistic models have been created to predict the risk of developing early-onset (UBC9 (AUC = 0.88; Se-0.72; Sp-1)) and late-onset PE (SUMO 1 (AUC = 0.79; Se-0.8; Sp-0.77)) at 11–14 weeks of pregnancy.