Objective To investigate the correlation between the expressions of negative regulatory cell CD4⁺CD25⁺T and its related cytokines in peripheral blood and bacterial infection of patients with chronic obstructive pulmonary disease (COPD). Methods Sixty-six COPD patients admitted between January 2018 and December 2019 were included as the research subjects, including 36 patients with acute exacerbation of COPD (AECOPD) and 30 patients with stable COPD. Another 30 healthy people undergoing physical examination during the same period were included in control group. The expression levels of CD4⁺CD25⁺ regulatory T cell and its related cytokines [interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-γ (IFN-γ)] in the peripheral blood samples were detected among the included subjects. The relationship between levels of related indicators and presence or absence of bacterial infection in COPD and the efficacy of predicting infection were analyzed. Results The levels of CD4⁺, CD4⁺CD25⁺ and IFN-γ/IL-4 in patients with AECOPD and patients with stable COPD were lower than those in control group (P<0.05), while the levels of IL-4 and IL-10 were higher than those in control group (P<0.05). The IFN-γ level of AECOPD patients was higher than that of control group (P<0.05). The levels of CD4⁺ and CD4⁺CD25⁺of AECOPD patients were lower than those of stable COPD patients (P<0.05), while the levels of IL-4, IL-10 and IFN-γ were all higher than those of stable COPD patients (P<0.05). The levels of CD4⁺ and CD4⁺CD25⁺were negatively correlated with IL-4 and IFN-γ (P<0.05), and the CD4⁺level was negatively correlated with IL-10 (P<0.05). The CD4⁺ level in COPD patients with infection was lower than that in patients without infection (P<0.05), while the levels of IL-4 and IFN-γ were higher than those in patients without infection (P<0.05). The CD4⁺CD25⁺level of COPD patients with Gram-negative bacteria infection was lower than that of patients without infection (P<0.05), while the IL-10 level was higher than that of patients without infection (P<0.05). CD4⁺, IL-4, IL-10 and IFN-γ were effective indicators in predicting bacterial infection in COPD patients (P<0.05), and IL-4 and IFN-γ had higher efficacy. Conclusions CD4⁺, CD4⁺CD25⁺ T cell and related cytokines are involved in the occurrence and development of COPD and bacterial infection in patients. Monitoring changes of those levels is helpful to provide information for clinical diagnosis and treatment.