The aim of this study was to analyze the phenotype of circulating dendritic cells (DCc) in rheumatoid arthritis (RA) patients before and after treatment with infliximab (at 24 h and 6 months) and the correlation between these changes and the clinical response to treatment. Sixteen patients with RA were recruited and clinical status was determined using the Disease Activity Score 28 (DAS28). All patients had active disease (mean DAS28 = 5.96) and were suitable for treatment with infliximab. Samples of peripheral venous blood were obtained before administration of the first dose of infliximab and again at 24 h and 6 months after treatment. DCc populations were analyzed by flow cytometry. At 24 h, there were no differences in the clinical status of the patients. However, we found a decrease in CD11c+ and, to a lesser extent, CD123+ DCc percentages. The expression of CD83, the most important activation marker for DC, was also shown to be decreased 24 h after infliximab therapy. After 6 months of treatment, all patients showed significant clinical improvement (mean DAS28 = 3.64, p < 0.001) and expression of the activation marker on DCc remained low. In conclusion, this study supports the role of tumor necrosis factor (TNF)-alpha blockade in preventing the maturation of DCc and in reducing the expression of their activation markers. Although the clinical response to infliximab was not observed after 24 h, DCc activation was strongly reduced by anti-TNF-alpha therapy. After 6 months of treatment, current data show a less active phenotype of DCc associated with clinical improvement in all patients in the study.