Background: Until now, the relationship between asprosin and soluble E-selectin (sE-selectin) as well as the role of asprosin in diabetes are still unclear. This work aimed to assess the relationship between fasting serum asprosin and markers of endothelial dysfunction and metabolic parameters, namely, sE-selectin, fasting insulin, fasting plasma glucose (FPG), HOmeostatic Model Assesment – Insulin Resistance (HOMA-IR), fasting lipid profile, and glycated hemoglobin (HbA1c) among people with different spectra of glycemia including normal subjects, impaired glucose tolerance (IGR), and subjects with type 2 diabetes mellitus (T2DM). Methods: Ninety subjects were recruited and divided according to the American Diabetes Association (ADA) diagnostic criteria into three groups; subjects with type 2 diabetes mellitus (n = 30), subjects with impaired glucose resistance (n = 30), and control subjects (n = 30). All groups were subjected to thorough history taking, physical examination, and laboratory investigation, involving fasting asprosin, sE-selectin, and HOMA-IR. Results: The univariate analysis showed a significant positive correlation between asprosin and glycemic parameters, insulin resistance, obesity parameters, and endothelial dysfunction in the three groups. However, multivariate analysis showed that triglycerides and sE-selectin are the most independent factors affecting asprosin. Univariate analysis for parameters affecting sE-selectin showed that asprosin is significantly correlated with sE-selectin, and multivariate analysis revealed that asprosin was the most independent factor affecting sE-selectin. Conclusions: Our study showed a significant positive correlation between asprosin, glucose dysregulation, insulin resistance, and endothelial dysfunction.