Background: This study assessed the role of different immune phenotypes of T cells in virus-induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Material/Methods: The study involved 103 participants, including individuals with virus-induced AECOPD (n=32), non-virus-induced AECOPD (n=31), and stable COPD (n=20) and individuals who were healthy smokers (n=20). The immune phenotypes of T cells in peripheral blood were evaluated via flow cytometry analysis, and the differences were analyzed. Results: Patients with virus-induced AECOPD (virus group) had a higher COPD assessment test score on admission than those in the group with non-virus-induced AECOPD (nonvirus group; 25.6 +/- 3.8 vs 21.9 +/- 4.8, P=0.045). A lower CD4(+) human leukocyte antigen-DR (HLA-DR)(+) frequency was found in the peripheral blood of the virus group compared with the nonvirus group (2.2 vs 4.2, P=0.015), and the frequency of CD4(+) CD25(high) CD127(low) HLA-DR+ in CD4(+) in the virus group was lower than in the nonvirus group (1.1 vs 3.6, P=0.011). The CD3(+), CD4(+), CD8(+), CD4(+) central memory T cell, CD4(+) effector memory T cell (Tem), CD4(+) end-stage T cell, and CD8(+) Tem levels in lymphocytes of peripheral blood were lower in exacerbation groups relative to those in the stable COPD and healthy smoking groups, but similar between exacerbation groups. Similar frequencies and levels of T cells between different stagings of COPD were also identified. Conclusions: The expression of HLA-DR on the cell surface of CD4(+) regulatory T cells (Tregs) was lower in the peripheral blood of patients with virus-induced AECOPD. The expression of HLA-DR in CD4(+) Tregs suggested the effect of respiratory viruses on adaptive immunity of patients with AECOPD to some extent.