There has been an increasing number of studies concerning the multiple biological activities of polyphenolic compounds. In this present study, we determined the effect of chlorogenic acid (CRA), a polyphenolic compound, on septic arthritis caused by Candida albicans, a major etiological agent that causes fungal arthritis. To induce septic arthritis, an emulsified mixture of C. albicans cell wall and Complete Freund's Adjuvant (CACW/CFA) was injected into BALB/c mice via hind footpad route once a day for 3 days. Twenty-four hours after the final injection, in order to determine CRA effect, mice having the swollen footpad were given CRA (1 mg/dose/mouse) intraperitoneally every other day three times. The footpad edema was measured for 15 days. Results showed that the CRA treatment reduced approximately 40% of the edema at the peak of septic arthritis (P < 0.05). This anti-arthritic activity appeared to be mediated by a complete inhibition of nitric oxide (NO) production from macrophages and suppression of T-cells proliferation. Furthermore, CRA also inhibited growth of C. albicans yeast cells (P < 0.01) and caused no hemolysis. These data indicate that CRA, which has antifungal and anti-arthritic effects, can safely be administered into the blood circulation for treatment of septic arthritis due to C. albicans. In addition, in respect to antiseptic arthritis, it can be suggested that the anti-candidal effect of CRA may be helpful as an all-in-one treatment of the candidal arthritis.