OBJECTIVE: Metabolic syndrome is a condition that promotes atherosclerosis and increases the risk of cardiovascular mortality and morbidity. We evaluated whether leisure time physical activity is associated with the levels of inflammatory and coagulation markers, in people with metabolic syndrome. METHODS: From May 2001 to December 2002 we randomly enrolled 1514 men and 1528 women (>18 years old), without any clinical evidence of cardiovascular disease, stratified by age-gender (census 2001). The population of the study was divided into those who fulfilled the NCEP ATP III criteria for the metabolic syndrome (n=701 or 33% men and 13% women) and the rest of the participants (n=2341). We assessed the relationship between self-reported physical activity status and inflammatory, and coagulation markers [i.e., C-reactive protein (CRP), serum amyloid-A (SAA), interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, white blood cell (WBC) counts, and fibrinogen (FIB)], after taking into account the effect of several confounders. RESULTS: Of the non-metabolic syndrome group, 56% of men and 58% of women were classified as sedentary, while of the metabolic syndrome group 58% men and 72% women were sedentary. After controlling for various potential confounders we found that physically active individuals with the metabolic syndrome had 36% lower levels of CRP, 15% lower levels of WBC, 19% lower levels of SAA, 15% lower levels of TNF-alpha, 30% lower levels of IL-6 and 15% lower levels of FIB, compared to sedentary (all P<0.05). Similar results were observed in the non-metabolic syndrome group. CONCLUSIONS: The adoption of a physically active lifestyle is independently associated with lower levels of the investigated biomarkers in individuals with the metabolic syndrome. The latter may suggest a pathway for reducing cardiovascular events, even in high-risk people.