The metabolic response to eccentric exercise in healthy older adults is unknown. Therefore, substrate metabolism was examined in the basal state and after sustained hyperglycemia (180 min, 10 mM) in eight healthy, sedentary older [66 ± 2 yr; body mass index (BMI) of 25.5 ± 1.2 kg/m] and nine younger (23 ± 1 yr; BMI of 23.6 ± 1.7 kg/m) men, under control conditions and 48 h after eccentric exercise. Indirect calorimetry was performed to evaluate carbohydrate and lipid oxidation (C_ox and L_ox, respectively). Eccentric exercise caused muscle soreness and increased plasma creatine kinase in both groups of men (P < 0.02). Although a similar level of hyperglycemia was maintained in the two groups, glucose infusion rates were lower (P < 0.001) in the older men. Compared with basal levels, hyperglycemia stimulated an increase in C_ox and a decrease in L_ox during the control and exercise trials in the younger group (P < 0.03), but only during the control trial in the older subjects (P < 0.007). C_ox was unchanged after eccentric exercise in the younger men [4.00 ± 0.30 vs. 3.54 ± 0.44 mg · kg fat-free mass (FFM)¹ · min¹; exercise vs. control] but was suppressed by 20% in the older group (3.37 ± 0.37 vs. 4.21 ± 0.23 mg · kg FFM¹ · min¹; P < 0.04). Moreover, L_ox was reduced by 38% in the younger subjects (0.47 ± 0.09 vs. 0.76 ± 0.10 mg · kg FFM¹ · min¹; P< 0.03) but was augmented by 89% in the older group (0.68 ± 0.11 vs. 0.36 ± 0.08 mg · kg FFM¹ · min¹; P < 0.04). In addition, hyperglycemia-stimulated C_ox, L_ox, and respiratory exchange ratio responses to eccentric exercise were related to abdominal adiposity (r = 0.57, P < 0.04, r = 0.68, P < 0.02 and r = 0.60, P < 0.02, respectively). Despite normal glucose tolerance and the absence of obesity per se, older men experience a reduction in carbohydrate oxidation in response to hyperglycemia after eccentric exercise.