Recent technological advances offer an opportunity to further elucidate the complex cytokine network in Major Depressive Disorder (MDD). Twenty cytokines were simultaneously assessed in 49 individuals with MDD and 49 age and gender matched controls. Multiple pro-inflammatory and two anti-inflammatory cytokines were significantly elevated in the MDD sample, including an antidepressant naïve subset. These data support a generalized chronic inflammatory state in MDD, and implicate additional cytokines and chemokines previously linked to cardiovascular disease.