Objective: The natural history of essential hypertension entails a sequence of neuro-endocrine alterations in the human body, which possibly result in body composition and compartment changes that can be detected using bio-impedance analyzers (BIA). Indeed, hypertension may be caused by chronically increased activity of the stress axis and/or renin-angiotensin system via pleiotropic mechanisms, including increased vasoconstriction and salt and water retention. Methods: This was a pilot, two-Center, case-control, cross-sectional study, whose main aim was to evaluate body composition and compartment changes in patients with newly diagnosed untreated essential hypertension using advanced bioimpedometry (BIA-ACC and TomEEx devices, Biotekna Co, Venice, Italy). Psychometric questionnaires (DASS21 and PSS-14 questionnaires) were also administered. Twenty untreated patients  with essential hypertension and twenty  normotensive age-, gender- and weight- matched controls agreed to participate after meeting the inclusion criteria of the study. Results: The psychometric scores were in the normal range in our hypertensive patients [MdnDASS21DEPRESSION = 8.40, MdnDASS21ANXIETY = 6.36, MdnDASS21STRESS = 12, MdnPSS14= 33], while their fat mass (Hypertensive group: Mdn = 38, Control group: Mdn = 42.75, U = 117, p = 0.024, r = 0.35) and lean body mass (Hypertensive group: Mdn = 62.00, Control group: Mdn = 57.25, U = 117, p = 0.025, r = - 0.35) were, respectively, lesser and greater than those of the controls. Using, impedometry, hypertensive patients demonstrated major body composition and compartment changes compared to controls. They had intracellular dehydration [IntraCellular Water – ICW (%Weight) - (Hypertensive group: Mdn = 53, Control group: Mdn = 56.86, U = 90, p = 0.0020, r = 0.46)], with increased extracellular water volumes [ExtraCellular Water – ECW (%Weight) - (Hypertensive group: Mdn = 47, Control group: Mdn = 43.14, U = 90, p = 0.0023, r = -0.468)], largely deviating from the control group. They also had major differences in potassium and magnesium homeostasis, with a significant augmentation of extracellular potassium (ECK+) as percent of total body potassium (TBK) (Hypertensive group: Mdn = 2.35, Control group: Mdn = 1.96, U = 72, p = 0.0003, r = - 0.545) and a reduced K+/Mg2+ ratio (Hypertensive group: Mdn = 4.5, Control group: Mdn = 4.63, U = 72, p = 0.0042, r = 0.44). Regional spectroscopy (TomEEx) detected presence of increased water or “inflammation” in the entire abdominal area of the hypertensive group. Conclusions: We speculate that body water compartment shifts from the intracellular to the extracellular space, along with potassium loss and low magnesium may be related to the pathophysiology of hypertension. They may reflect a genetic/epigenetic predisposition to stress and/or renin-angiotensin system hyperactivity and/or action that usually presents with hypertension at mid-age.