We evaluated whole body and regional adipose tissue lipid kinetics and norepinephrine (NE) spillover during brief fasting in six lean [body mass index (BMI) 21 ± 1 kg/m²] and six upper-body obese (UBO; BMI 36 ± 1 kg/m²) women. At 14 h of fasting, abdominal adipose tissue glycerol and free fatty acid (FFA) release rates were lower (P = 0.07), but whole body glycerol and FFA rates of appearance (R_a) were greater (P < 0.05) in obese than in lean subjects. At 22 h of fasting, glycerol and FFA R_a increased less in obese (19.8 ± 7.0 and 87.1 ± 30.3 μmol/min, respectively) than in lean (44.2 ± 6.6 and 137.4 ± 30.4 μmol/min, respectively; P < 0.05) women. The percent increase in glycerol R_a correlated closely with the percent decline in plasma insulin in both groups (r ² = 0.85; P < 0.05). Whole body NE spillover declined in lean (P < 0.05) but not obese subjects with continued fasting, whereas regional adipose tissue NE spillover did not change in either group. We conclude that, compared with lean women, in UBO women 1) basal adipose tissue lipolysis is lower, but whole body lipid kinetics is higher because of their greater fat mass; 2) the increase in lipolysis during fasting is blunted because of an attenuated decline in circulating insulin; and 3) downregulation of whole body sympathetic nervous system activity is impaired during fasting.