Surgical aortic valve replacement (SAVR) remains an essential treatment option for patients with aortic stenosis (AS). Open-heart surgery requires the use of cardiopulmonary bypass (CPB), which triggers an inflammatory response that can lead to end-organ dysfunction and severe complications. Dexmedetomidine, a highly selective α2-adrenergic agonist, is widely used in anesthesia and intensive care medicine for its sedative, analgesic, and sympatholytic properties. This study aimed to investigate whether dexmedetomidine exerts a clinically relevant anti-inflammatory effect in patients undergoing open-heart surgery and to determine the optimal dose. A prospective, double-blind, placebo-controlled study was conducted, including 60 patients randomized into three groups according to dexmedetomidine dose. Inflammatory markers (IL-6, TNF-α), renal function, and other clinical parameters were analyzed at multiple time points. Statistical analyses were performed to assess differences between the groups. Dexmedetomidine administration significantly affected TNF-α levels 12 h after CPB (p = 0.033), while previously reported suppression of IL-6 was not observed. Dexmedetomidine was associated with lower opioid consumption before extubation and showed a tendency to reduce postoperative delirium. Diuresis was significantly increased on the first postoperative day in dexmedetomidine-treated patients (p = 0.003), with no significant changes in other renal parameters. The incidence of atrial fibrillation was highest in the control group and lowest in the high-dose dexmedetomidine group, though this difference was not statistically significant. These results suggest that dexmedetomidine influences inflammatory and clinical outcomes; however, further research is needed to confirm its long-term benefits and optimal dosing strategies.