The ability of cytokines to influence cerebral functions and to induce the development of behavioral alterations is well established in conditions of acute or chronic high-grade activation of the innate immune system. Recent evidence suggests that the release of these immune mediators during chronic low-grade endogenous inflammatory processes may also contribute to the development of behavioral alterations. Metabolic disorders, including obesity, type 2 diabetes and the metabolic syndrome, represent examples of those conditions which are both characterized by a chronic low-grade inflammatory state and an increased prevalence of behavioral disorders. In metabolic disorders, the increased production of acute-phase proteins and cytokines (e.g. C-reactive protein, interleukin-6 and tumor necrosis factor-α), but at relatively low levels, may promote and contribute to the development of behavioral symptoms, including depressive symptoms, cognitive impairment, fatigue, sleep problems and pain. This hypothesis is supported by a growing literature referring both to experimental and clinical findings that will be reviewed here.