The prevalence of chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) is increasing globally, yet their comprehensive impact on the immune system remains underexplored. This study aimed to provide a thorough assessment of the immune status of patients with COPD and tuberculosis (TB-COPD), including their pulmonary conditions, immune cell responses, and changes in lymphocyte subpopulations. A total of 151 patients with TB-COPD patients were included, and clinical data were compared between the TB-COPD group and a group of TB patients without COPD (TB-NCOPD). Lung imaging findings and peripheral blood immune cell levels were compared between the 2 groups. Flow cytometry was used to analyze the absolute counts of lymphocyte subpopulations. The incidence of pulmonary lobe lesions and cavitation in the TB-COPD group aged 70 years or older was significantly higher than that in the control group. At the immune cell level, patients with TB-COPD showed a significant reduction in total lymphocytes, CD4+ T lymphocytes and CD4+/CD8+ ratio. Regardless of COPD status, the CD4+ T cell count in the CMV-infected group was significantly lower than that in the uninfected group (P < .05). Additionally, the CD4+/CD8+ ratio in the COPD + TB CMV + group was significantly lower than that in the uninfected group. Analysis of lymphocyte subpopulations revealed a decrease in the counts of CD4+ T lymphocytes in patients with TB-COPD, potentially associated with the chronic inflammatory state induced by COPD. The one-month treatment outcomes showed that the improvement rate in the control group was 70.58%, which was significantly higher than the 38.92% in the COPD + TB group (P < .001). We observed a significant increase in the number of pulmonary cavity patients in the TB-COPD group, suggesting that COPD may be a potential risk factor for the formation of pulmonary cavities in patients with TB. At the immune cell level, TB-COPD patients showed a notable decrease in lymphocytes and CD4+ T lymphocytes, implying that COPD combined with pulmonary TB may significantly affect the immune system, leading to a reduction in the counts of key immune cells.