Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 54 10 2025 10 31 2212 2222 EN Yingjia Zhu Department of Gynecology, Hangzhou Women’s Hospital, Hangzhou, Zhejiang, 310000, China Feng Cheng Department of Orthopedics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, China WenHui Wang Department of Pathology, Hangzhou Women’s Hospital, Hangzhou, Zhejiang, 310000, China XinYun Yang Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, China Mingjie He Department of General Practice, Yiqiao Community Health Service Center, Hangzhou, Zhejiang 310000, China Zhiyin Zhang Department of Gynecology, Hangzhou Women’s Hospital, Hangzhou, Zhejiang, 310000, China LinLing Zhu Department of Gynecology, Hangzhou Women’s Hospital, Hangzhou, Zhejiang, 310000, China 2024 09 01 2025 04 23 Background: Postpartum depression (PPD) is influenced by immune factors, particularly immune cells. The causal relationship between these cells and PPD is unclear. Methods: Bidirectional two-sample Mendelian randomization (TSMR) analysis was performed to determine the causal relationship between immune cell characteristics and PPD. The main analysis method used was the inverse variance weighted (IVW) method. To ensure the robustness, heterogeneity, and horizontal pleiotropy of the results, a comprehensive sensitivity analysis was conducted. Results: Overall, 28 immune cell phenotypes were identified as causally related to the onset of PPD. Most of them were distributed in the B cell group and the Treg cell group. Further analysis revealed that 13 types of immune cells had a promoting effect on PPD, whereas 15 types of immune cells had a protective effect. In addition, the incidence of PPD was found to be causally related to CD62L on granulocyte [IVW: OR (95%): 1.183 (1.037 to 1.348), P = 0.012]. Conclusion: The study unveils the causal link between immune cells and susceptibility to postpartum depression from a genetic standpoint, providing new directions for drug development and precision medicine for PPD treatment. https://ijph.tums.ac.ir/index.php/ijph/article/view/36527 https://ijph.tums.ac.ir/index.php/ijph/article/download/36527/8679