The purpose of this cross-sectional study was to examine the association between the metabolic syndrome (MetS) and physical activity energy expenditure (PAEE) in overweight and obese sedentary postmenopausal women. The study population consisted of 137 overweight and obese sedentary postmenopausal women (age, 57.7 +/- 4.8 years; BMI, 32.4 +/- 4.6 kg.m(-2)). Subjects had the MetS if 3 out of the following 5 criteria were met: visceral fat > 130 cm2, high-density lipoprotein (HDL) cholesterol < 1.29 mmol.L(-1), fasting triglycerides > or = 1.7 mmol.L(-1), blood pressure > or = 130/85 mmHg, and fasting glucose > or =5.6 mmol.L(-1). We measured (i) body composition (by dual-energy X-ray absorptiometry); (ii) visceral fat (by computed tomography); (iii) insulin sensitivity (using the hyperinsulinemic-euglycemic clamp); (iv) plasma lipids, fasting glucose, and insulin, as well as 2 h glucose during an oral glucose tolerance test; (v) resting blood pressure; (vi) peak oxygen consumption (VO2 peak); (vii) PAEE (using doubly labeled water); and (viii) lower-body muscle strength (using weight-training equipment). Forty-two women (30.7%) had the MetS in our cohort. Individuals without the MetS had significantly higher levels of PAEE (962 +/- 296 vs. 837 +/- 271 kcal.d(-1); p < 0.05), VO2 peak (18.2 +/- 3.0 vs. 16.7 +/- 3.2 mL.min(-1).kg(-1); p < 0.05), and insulin sensitivity, as well as significantly lower levels of 2 h glucose and central lean body mass. No differences in total energy expenditure, resting metabolic rate, and muscle strength between groups were observed. Logistic regression analysis showed that 2 h glucose (odds ratio (OR): 1.50 (95% CI 1.17-1.92)), central lean body mass (OR: 1.17 (95% CI 1.05-1.31)), and PAEE (OR: 0.998 (95% CI 0.997-1.000)), but not VO2 peak and (or) muscle strength, were independent predictors of the MetS. Lower levels of PAEE and higher levels of 2 h glucose, as well as central lean body mass, are independent determinants of the MetS in our cohort of overweight and obese postmenopausal women.