Objective To investigate the association between tumor necrosis factor-α (TNF-α), macrophage migration inhibitory factor (MIF), soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6) levels and cardiac diastolic function in patients with BD. Methods From January to May 2024, a total of 88 patients with BD were recruited from The Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University as the case group (including 32 in the manic episode group, 14 in the depressive episode group, and 42 in the remission phase group), along with 44 healthy individuals as the control group. Plasma TNF-α, sIL-2R, MIF, and IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Cardiac diastolic function was assessed by the ratio of early diastolic velocity of mitral inflow (E) to the average early diastolic tissue velocity at the lateral and septal mitral annulus (e′) (E/e′), as determined by color Doppler echocardiography. Results Statistically significant differences were observed in plasma TNF-α, sIL-2R, MIF, and IL-6 levels between BD patients and healthy controls (P＜0.001). Patients in remission also showed significant differences in these cytokine levels compared to healthy individuals (P＜0.001). No significant differences were found in plasma TNF-α, sIL-2R, MIF, and IL-6 levels between patients with manic and depressive episodes (P=0.174; P=0.716; P=0.622; P=0.772). Significant differences in plasma TNF-α, sIL-2R, MIF, and IL-6 levels were noted between patients in remission and those with manic episodes (P＜0.001), as well as between patients in remission and those with depressive episodes (P＜0.001; P=0.002; P=0.024; P＜0.001).After adjusting for confounding factors, plasma TNF-α, sIL-2R, MIF, and IL-6 levels in the BD patient group were significantly positively correlated with the mean E/e′ value (P＜0.001; P＜0.001; P=0.005; P＜0.001). In patients in remission, plasma TNF-α, sIL-2R, and IL-6 levels were significantly positively correlated with the mean E/e′ value (P＜0.001), while plasma MIF level showed no significant correlation with the mean E/e′ value (P=0.268). No significant correlation was found between plasma TNF-α, sIL-2R, MIF, and IL-6 levels and the mean E/e′ value in patients experiencing manic or depressive episodes. In both the case group and patients in remission, multiple regression analysis revealed a significant correlation between plasma TNF-α, IL-6, and E/e′ values（P=0.037；P＜0.001；P=0.040；P=0.006）. Conclusion Levels of TNF-α and IL-6 showe a significant association with cardiac diastolic function in patients with bipolar disorder (BD)