The serum high-sensitivity C-reactive protein (hsCRP) levels in patients with major depressive disorder and bipolar I disorder in acute phases were investigated. During a 1-year period, a total of 67 participants including 23 patients with major depressive disorder, 13 patients with bipolar I disorder (manic episode) and 31 healthy controls were recruited in this study. The diagnoses of mental disorders in participants were made by one psychiatrist according to the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). Both patient groups with major depression and bipolar disorder had higher mean serum hsCRP levels than the healthy control group. Using analysis of covariance with age adjustment, patients with bipolar I disorders still had significantly higher hsCRP levels than healthy controls (P=0.043). However, patients with major depression did not have significantly higher hsCRP levels than healthy controls (P=0.172). These results suggest that patients with bipolar I disorder might have a more severe inflammation reaction than patients without major depression. However, larger samples and adequate statistical methods are needed to prove these results.