We evaluated the association of physical activity and diet with C-reactive protein (CRP) levels among subjects with abdominal obesity. During 2001-2002, we enrolled 625 men (18 to 87 years old) and 712 women (18 to 89 years old) with abdominal obesity (waist-to-hip ratio > or =0.95 in men and > or =0.8 in women) from the Attica area, Greece. The sampling was stratified by the age-gender distribution of the region (census 2001). Among several variables, we also measured plasma high-sensitivity CRP, physical activity status, dietary habits, blood lipids, and blood pressure levels. Adherence to the Mediterranean diet was evaluated through a diet score (0 to 55) that assessed the inherent characteristics of the diet. Compared with those with low CRP levels, subjects with high CRP levels (ie, >3.0 mg/L) were physically inactive (P = .01), were less likely to adopt the Mediterranean diet (P = .008), had higher glucose levels, had a higher prevalence of hypertension, had a lower high-density lipoprotein cholesterol, and had increased smoking habits and higher anthropometric indices (all P < .05). Moreover, adoption of the Mediterranean diet in combination with medium physical activity seems to reduce the likelihood of having high CRP levels by 72% (P = .018), irrespective of smoking and various clinical and biological characteristics. Among subjects with abdominal obesity, low-grade systemic inflammation appears to be associated with the adoption of an unfavorable lifestyle, including physical inactivity and unhealthy dietary habits, as well as increased blood pressure levels and low high-density lipoprotein cholesterol.