Regulation of food intake involves a variety of homeostatic and hedonic components controlled by a system of hunger and satiety signals originating in both peripheral and central pathways. In the present study, the relevance and time course of physiological responses reflecting the status of the autonomic nervous system, specifically the sympathetic— parasympathetic balance, was evaluated in relation to food intake and perceived satiety in humans. Eighteen subjects were exposed individually to a lunch-induced hunger–satiety shift, throughout which sensory ratings, physiological, and biochemical characteristics were obtained at 15 min intervals. Subjects rated, on visual analogues scales (VAS), their feeling of satiety, desire to eat, fullness, and hunger on separate questionnaires. Using non-invasive monitoring, heart rate, heart rate variability and blood pressure, as well as cortisol levels and a-amylase activity in saliva were measured. Across subjects and throughout the hunger-satiety shift, all four sensory ratings correlated with heart rate and salivary a-amylase, and reflected high activity of the sympathetic nervous system during the satiety state. Among men cortisol levels were negatively correlated with age and BMI. Finally, neither oral activities like chewing and swallowing nor orosensory stimulation by food, as tested with modified sham feeding, were found to contribute to any extent to the instant heart rate increase after food consumption. In conclusion, after meal ingestion, specific patterns and critical alterations of physiological characteristics reveal a high sympathetic tone that can be used as an objective determinant of the state of satiety.