Purpose: This study aimed to clarify the effect of severe hyperemesis gravidarum (sHG) on maternal vascular endothelial health with evaluation of soluble adhesion molecules. Method: The study population consisted of two groups of pregnant participants between 18 and 35 years of age who were between 5 and 13 weeks of gestation: sHG group and a healthy control group. A group of 26 participants whose pregnancies were complicated by sHG was compared with 26 healthy participants regarding serum levels of the soluble adhesion molecules such as E-selectin, soluble intracellular cell adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule one (sVCAM-1), as well as other biochemical markers. The two groups had similar baseline characteristics. Results: Maternal baseline characteristics were similar in both groups. Serum levels of E-selectin (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were higher in the sHG group compared with the control group. Higher blood urea nitrogen, creatinine, and sodium levels, serum osmolarity, and urine density (p < .001, < .001, .006, .041, and .001, respectively) were also observed in the sHG group compared with the control group. Conclusions: The findings of this study indicated that sHG could impact endothelial cell function and these changes represented hypovolemia and dehydration caused by severe vomiting. Large-scale studies are required to understand the clinical importance of this finding regarding the long-term consequences and underlying mechanisms of elevated sICAM-1, sVCAM-1, and sE-selectin synthesis.