The aim of the present study is to evaluate the role of CRP and Total Cholesterol (TC) in patients suffering from type I Bipolar Disorder (BD-I). Moreover, the goal is to elucidate possible CRP and TC differences in different phases of BD-I: acute mania, euthymia and bipolar depression. Medical records of 90 BD-I patients (30 patients with acute mania, 30 in euthymic state, full remission, and 30 in depressive phase) were reviewed to evaluate serum CRP and TC levels. Laboratory data of 30 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. CRP levels were higher in acute mania and depressive phase subgroups when compared to healthy controls. CRP was positively associated with BRMRS and YMRS scores in acute mania and with HAM-D in depressive phase subgroups. TC levels were lower in all clinical groups compared to controls. TC levels were negatively correlated to BRMRS, YMRS and HAM-D. In conclusion, the results of the present study support the notion that CRP and TC may be altered in patients with BP-I.