The metabolic syndrome (MetS) is associated with a pro-inflammatory milieu that may partially account for its association with an increased cardiovascular risk. We aimed to (1) evaluate the serum concentrations of twelve cytokines and growth factors (epidermal growth factor (EGF), interferon-γ (IFN-γ), IL-1α/-1β/-2/-4/-6/-8/-10, monocyte chemoattractant protein-1 (MCP-1), TNF-α and vascular endothelial growth factor (VEGF)) in 303 individuals with or without the MetS; and (2) explore their relationship with the presence of the MetS. Patients with the MetS had significantly higher serum concentrations of IFN-γ, EGF, IL-1α/-1β/-2/-4/-6/-8/-10, MCP-1 and TNF-α, whilst serum VEGF concentrations were markedly lower compared with the control group (e.g. 38·55 v. 82·18 pg/ml; P< 0·05). Amongst these parameters, IFN-γ and IL-1α emerged as the most significant independent predictors of the MetS. In conclusion, our findings demonstrate that patients with the MetS had an altered blood cytokine and growth factor profile that may partially account for its adverse clinical outcomes. Further prospective studies in larger multi-centre settings are required to unravel the role and association of the emerging biomarkers with the MetS and their implication in therapeutic intervention.