Objective: To investigate the changes and clinical significance of T lymphocyte subsets and mitochondrial damage in patients with bipolar disorder (BD). Methods: 102 BD patients were retrospectively selected as the observation group. According to the evaluation results of the Clinical Global Impressions-Severity scale at admission, the patients were classified into a mild group (n=41), moderate group (n=35), and severe group (n=26). All patients received standardized treatment with quetiapine fumarate tablets combined with amitriptyline hydrochloride tablets for 8 weeks after admission, and were categorized into an effective treatment group (n=81) and an ineffective treatment group (n=21) based on treatment response results. 90 healthy subjects undergoing physical examination were included in the control group. T lymphocyte subsets (percentage of CD45+ lymphocytes, percentage of CD3+ T cells) and mitochondrial damage indexes of helper T lymphocytes (Th) and cytotoxic T lymphocytes (Ts) were detected and compared. A receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of related indicators. Results: Compared with the control group, the percentages of CD45+ lymphocytes and CD3+ T cells in the observation group were lower, while the positive rates of Th and Ts mitochondrial damage indexes were higher (P<0.05). Compared with the mild group, the percentage of CD45+ lymphocytes and percentage of CD3+ T cells in the moderate group and the severe group were lower in turn, while the positive rate of Th cell mitochondrial damage index and positive rate of Ts cell mitochondrial damage index were higher in turn (P<0.05). ROC curve analysis revealed that the areas under the curves (95% CI) of the above indicators for predicting severe BD were 0.672 (0.536~0.807), 0.628 (0.492~0.763), 0.706 (0.595~0.818), and 0.700 (0.586~0.815) respectively, and the area under the curve (95% CI) of the combined prediction of the four indicators was higher at 0.846 (0.761~0.931). The percentage of CD45+ lymphocytes and percentage of CD3+ T cells in the ineffective treatment group were lower compared with those in the effective treatment group, while the positive rates of Th and Ts cell mitochondrial damage indexes were higher (P<0.05). ROC curve analysis showed that the areas under the curves (95% CI) of the above indicators for predicting BD treatment ineffectiveness were 0.892 (0.803~0.982), 0.858 (0.759~0.956), 0.785 (0.691~0.879), and 0.773 (0.672~0.875), respectively, and the combined prediction value of the four indicators was higher, with an area under the curve (95% CI) of 0.981 (0.727~0.989). Conclusion: BD patients have immune dysfunction. T lymphocyte subsets and mitochondrial damage indexes can be used as effective indicators to evaluate the disease condition and treatment response.