Activated T regulatory (T_reg) cells are potent suppressors that mediate immune tolerance. We investigated the relationship between activated T_reg cells and the progression of human colon cancer. We designed a cross‐sectional study of CD4⁺Foxp3⁺ T cells from peripheral blood, primary tumor and nontumor colon tissue of 42 patients with colon cancer and correlated the percentages of different subgroups of T_reg cells with colon cancer stage. The phenotypes, cytokine‐release patterns and suppression ability of these T_reg cells were analyzed. We found that T_reg cells increased significantly in both peripheral blood and cancer tissue. In addition, the T_reg cells expressed significantly lower levels of CCR7, CD62L and CD45RA in comparison to normal volunteers. Further dividing T_reg cells into subgroups based on Foxp3 and CD45RA expression revealed that both activated T_reg cells (Foxp3^hiCD45RA⁻) and nonsuppressive T_reg cells (Foxp3^loCD45RA⁻), but not resting T_reg cells (Foxp3^lowCD45RA⁺), increased in the peripheral blood and cancer tissue of patients with colon cancer. Only the activated T_reg cells expressed significantly higher levels of tumor necrosis factor receptor 2 and cytotoxic T‐cell antigen‐4. Activated T_reg cells, however, secreted significantly lower levels of effector cytokines (interleukin‐2, tumor necrosis factor‐α and interferon‐γ) than did resting T_reg cells and nonsuppressive cells upon ex vivo stimulation. Activated, but not resting, T_reg cells in cancer tissue correlated with tumor metastases. In summary, we confirmed that activated T_reg cells are a distinct subgroup with effector memory phenotype and fully functional regulatory activity against human colorectal cancer immunity.