Food ingestion can influence autonomic nervous system activity. This study compares the effects of 2 different isoenergetic meals on sympathetic nervous system (SNS) activity, assessed by heart rate variability (HRV) and plasma norepinephrine (NE) levels, in lean and obese women. Fifteen lean and 15 obese healthy women were examined on 2 occasions: after a carbohydrate (CHO)-rich and after a fat-rich test meal. Measurements of blood pressure, heart rate, resting energy expenditure, plasma glucose, lipids, insulin, leptin, and NE, as well as spectral analysis of the HRV, were performed at baseline and every 1 hour for 3 hours after meals. At baseline, obese women had higher SNS activity than lean controls (higher values of low-to-high frequency ratio [LF/HF], 1.52 ± 0.31 v 0.78 ± 0.13, P = .04; and plasma NE levels, 405.6 ± 197.9 v 240.5 ± 95.8 pg/mL, P < .0001). After the CHO-rich meal a greater increase in LF/HF and in plasma NE levels was observed in lean, compared to obese women (1.21 ± 0.6 v 0.32 ± 0.06, P = .04; and 102.9 ± 35.4 v 38.7 ± 12.3 pg/mL, P = .01, respectively), while no differences were observed after the fat-rich meal. Meal-induced thermogenesis was higher after the CHO-rich as compared to the fat-rich meal and was comparable between lean and obese women. Changes in HRV were not associated with the thermogenic response to the test meals. In conclusion, consumption of a CHO-rich meal causes greater cardiac SNS activation in lean than in obese women, while fat ingestion does not result in any appreciable change in either group. SNS activation does not appear to influence the thermic effect of the food in either lean or obese women.