Purpose: Post-meal cardiometabolic responses are critical for health, and may be influenced by physical activity. The objective of this study was to investigate the effect of habitual physical activity level on the metabolic, autonomic nervous system and cardiovascular responses to a balanced meal in healthy men. Methods: 12 active and 12 inactive healthy males, matched for age and body composition, attended the laboratory in fasting condition. Participants were asked to sit quietly and comfortably in an armchair for the whole duration of the experiment (~ 2h30). Metabolic, autonomic nervous system and cardiovascular measurements were performed in fasting conditions, and at regular intervals until one hour after the end of a balanced breakfast. Results: No significant difference was observed between groups in glycaemia or energy expenditure throughout the experiment. Fat oxidation rate was significantly higher one-hour post-meal in active vs inactive men (Respiratory Quotient: 0.78 ± 0.04 vs 0.88 ± 0.03; p textless 0.01). Heart rate was significantly lower in active compared to inactive individuals (p textless 0.001) throughout the experiment and active participants displayed significantly enhanced vagal tone one-hour post-meal (square root of the sum of successive differences between adjacent normal R-R intervals squared: 72.4 ± 27.9 vs 46.4 ± 14.1 ms; p textless 0.05). Conclusion: In healthy men, habitual physical activity level seems discriminant to decipher specific profiles in terms of cardiometabolic responses to a meal. Overall, it may suggest pre-signal cardiometabolic impairments in healthy inactive individuals and highlight the need to consider primary prevention in inactive subjects as a key factor for health management.