Therefore, we evaluated a cohort of well‐characterized DENV, ZIKV, or DENV/ZIKV‐infected patients and DENV‐exposed healthy donors. Molecular and serological methodologies confirmed all infections. Even without specific in vitro antigenic stimulation, DENV, ZIKV, and DENV/ZIKV infections induced expression of CCR5, CX3CR1, and CXCR3 on CD4+ and CD8+ T cells, indicating an activated status of these cells. However, DENV/ZIKV coinfection decreased the ability of CD4+ T cells to produce IFNγ+, TNF+, TNF+ IFNγ+, and TNF+ IL2+, compared to DENV and ZIKV infections. Finally, a hyporesponsiveness of effector/memory T cells in most of acute patients against DENV NS1 specific antigen might occur due to a clonal exhaustion. We would like to emphasize the potential impact of coinfection on the immune response from a human host.