Recent evidence suggests that peripheral markers related to oxidative stress, inflammation and neurotrophins may be altered during mood episodes in bipolar disorder. These can be seen as proxies of peripheral toxicity or markers of illness activity. Here we report an en bloc assessment of a set of previously described biomarkers in different mood states (n = 60) as well as in healthy subjects (n = 80). To make the point that these are ominous changes, we obtained the same measures from a group of septic patients (n = 15) as a "positive" control group. In this sample, we measured serum levels of brain derived neurotrophic factor, neurotrophin 3, tumor necrosis factor α, interleukin 6, interleukin 10, total reactive antioxidant potential, thiobarbituric acid reactive substances and protein carbonyl content. Several of the markers discriminated between the bipolar and control groups, especially when patients were in acute episodes. In some cases, toxicity was as high in bipolar disorder as that seen in patients with sepsis. We believe these findings highlight the potential of using biomarkers to assess illness activity in bipolar disorder.