Objectives  Adipose tissue‐derived inflammation may contribute to metabolic alterations and eventually to the metabolic syndrome (MetS). The purpose of this study was to: (1) examine the role of adipocytokines in the association between obesity and the MetS and (2) to determine whether the association is different in obese and non‐obese persons.

Design  Cross‐sectional population‐based InCHIANTI study.

Subjects  A total of 944 community‐dwelling adults aged 65 years and older living in Tuscany, Italy.

Measurements  Obesity was defined as body mass index ≥30 kg/m² and MetS as ≥3 of the ATP‐III criteria. Circulating levels of C‐reactive protein, interleukin (IL)‐6, IL‐1 receptor antagonist (IL‐1ra), IL‐18, tumour necrosis factor (TNF)‐α R1, adiponectin, resistin and leptin were measured. Additionally, insulin resistance was determined using the homeostasis model assessment (HOMA‐IR).

Results  The prevalence of the MetS was 32%. Both overall and abdominal obesity were significantly associated with the MetS after adjusting for inflammatory cytokines, adipokines and lifestyle factors. After adjusting for multiple confounders and HOMA‐IR, IL‐1ra, TNF‐α R1 and adiponectin (P < 0·05) remained significantly associated with the MetS. Having multiple cytokines in the highest tertile increased the likelihood of having the MetS in both obese (P for trend 0·002) and non‐obese persons (P for trend 0·001) independent of insulin resistance.

Conclusions  Non‐obese and obese individuals who develop an intense pro‐inflammatory state may be more prone to develop the MetS than those with lower levels of inflammation.