BACKGROUND: Premedication in outpatient dental interventions normalizes pain sensitivity and emotional state of patients. Inhalation of xenon-oxygen mixture can be an effective means for it. AIM: To study the effect of xenon premedication on pain sensitivity in patients with outpatient dental interventions. MATERIALS AND METHODS: Twenty patients were studied. Emotional and personal characteristics of patients were determined using the Eysenck test, Spielberger–Khanin personal anxiety scale, and hospital scale of anxiety and depression. Pain sensitivity was assessed using pain thresholds and somatosensory evoked potentials of the brain before and after inhalation of xenon-oxygen mixture at a concentration of 30/70 for 3 minutes. RESULTS: According to the results of psychological testing, all examined patients were characterized by a stable psychological sphere and predominantly lowered anxiety and constituted a group with insignificantly different emotional and personal characteristics. Before inhalation, pain sensitivity in patients varied significantly. After inhalation, multidirectional changes in pain sensitivity occurred, which were expressed in a decrease and an increase in pain sensitivity thresholds and the degree of activation of brain structures. CONCLUSION: Preoperative stress can both exacerbate and reduce pain sensitivity in patients. The use of inhalation of a xenon-oxygen mixture at a concentration of 30/70 for 3 minutes as a premedication causes multidirectional changes in the sensitivity of tissues and organs in the maxillofacial region in patients before outpatient dental interventions, which may be caused by a change in the activity of endogenous antinociceptive (analgesic) system.