Age-related changes in leptin and adiponectin levels remain controversial, being affected by inconsistent normalisation for adiposity and body fat distribution in the literature. In a cross-sectional study on 210 Caucasians (127 women, eighty-three men, 18-78 years, BMI 16.8-46.8 kg/m²), we investigated the effect of age on adipokine levels independent of fat mass (FM measured by densitometry), visceral and subcutaneous adipose tissue volumes (VAT and SAT assessed by whole-body MRI). Adiponectin levels increased with age in both sexes, whereas leptin levels decreased with age in women only. There was an age-related increase in VAT (as a percentage of total adipose tissue, VAT%TAT), associated with a decrease in SAT(legs)%TAT. Adiposity was the main predictor of leptin levels, with 75.1 % of the variance explained by %FM in women and 76.6 % in men. Independent of adiposity, age had a minor contribution to the variance in leptin levels (5.2 % in women only). The variance in adiponectin levels explained by age was 14.1 % in women and 5.1 % in men. In addition, independent and inverse contributions to the variance in adiponectin levels were found for truncal SAT (explaining additional 3.0 % in women and 9.1 % in men) and VAT%TAT (explaining additional 13.0 % in men). In conclusion, age-related changes in leptin and adiponectin levels are opposite to each other and partly independent of adiposity and body fat distribution. Normalisation for adiposity but not for body fat distribution is required for leptin. Adiponectin levels are adversely affected by subcutaneous and visceral trunk fat.