Objective: Severe fever with thrombocytopenia syndrome (SETS) is an emerging infectious disease with high mortality. T cell deficiency has recently been described, but the changes in T cell functionality during acute SETS virus (SETSV) infection and the mechanisms leading to T lymphocyte death remain largely unknown. This study was conducted to evaluate T cell functionality and the expression of apoptotic/ proliferation and activation/inhibition markers during acute SETSV infection. Methods: Twenty-eight surviving SETS patients were sequentially sampled during their entire hospital stay. SETSV RNA copies were investigated using real-time RT-PCR. The expression levels of apoptotic markers (annexin V and CD95) and proliferation and activation markers (Ki-67, HEA-DR, and CD25) and the expression levels of programmed cell death-1 (PD-1), interferon gamma (IFN-gamma), and granzyme B in T cells were evaluated by flow cytometry for the SETS patients. Results: In parallel with T cell depletion, higher annexin V and CD95 expression was observed in SETS patients. Additionally, the expression levels of Ki-67, HLA-DR, CD25, and PD-1 and the levels of IFN-gamma and granzyme B in T lymphocytes were markedly increased in the SFTS patients. Conclusions: T cell proliferation, activation, and functional enhancement were apparent despite the observation of T cell apoptosis, suggesting that these processes are involved in the complex protective response to SFTSV infection. (C) 2018 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.