Adiponectin may play an important role in the regulation of body weight, insulin resistance, and cardiovascular disease. The aim of this study was to evaluate the distribution of adiponectin in a Mediterranean adult population and its relationship with cardiovascular risk factors and metabolic syndrome. A cross-sectional study was performed in a representative sample of 1023 subjects from a Spanish Mediterranean population. Individuals with the metabolic syndrome were identified using the diagnostic criteria of the Adult Treatment Panel III. Anthropometric parameters were measured, and biochemical analyses were performed in fasting conditions. Plasma insulin levels were measured and homeostasis model assessment of insulin resistance was calculated. Plasma adiponectin levels were measured by a commercial radioimmunoassay. Median levels of adiponectin were significantly higher in women than in men after adjusting for differences in body mass index. However, no differences in adiponectin plasma levels were observed in relation to age. Significantly lower levels of adiponectin were also observed in women with obesity, abdominal obesity, hyperglycemia or diabetes, low high-density lipoprotein cholesterol, hypertriglyceridemia, or metabolic syndrome. In men, only those with obesity, abdominal obesity, low high-density lipoprotein cholesterol, hypertriglyceridemia, or metabolic syndrome showed significantly lower plasma levels of adiponectin. In a stepwise multivariate analysis, sex, waist circumference, serum C-reactive protein serum levels, and homeostasis model assessment of insulin resistance explained 23.4% of its variability. In conclusion, adiponectin plasma levels are more closely related to the components of the metabolic syndrome in women than in men in a Mediterranean population.