Myeloproliferative neoplasms (MPN) are chronic hematological disorders marked by the abnormal proliferation of bone marrow cells. The most commonly encountered forms are polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET). These disorders are generally associated with increases in blood components, which can lead to conditions like splenomegaly, thrombosis, bleeding tendencies, and a heightened risk of progressing to acute leukemia. Previous research has indicated a possible link between immune cells and MPN, yet this association is still poorly understood. This study seeks to elucidate the causal relationship between immune cell characteristics and the development of MPN. In this study, we employed Mendelian randomization (MR) to investigate potential causal links between 731 immune cell traits and the risk of developing MPN, leveraging data from genome-wide association studies (GWAS). To ensure the robustness of our findings, we conducted extensive sensitivity analyses to assess heterogeneity and detect any pleiotropic effects. Moreover, we implemented a false discovery rate (FDR) correction to mitigate the risk of false positives that may result from the multiple hypothesis testing, thereby adjusting for any statistical biases due to multiple comparisons. The immune phenotype IgD on IgD+ CD24- B cells demonstrated a statistically significant protective effect against MPN (PFDR = 0.047). Upon adjusting the significance threshold to PFDR < 0.20, 16 immune cell phenotypes were significantly associated with MPN. Among these, 11 were found to exert a protective effect against MPN, 5 phenotypes were associated with an elevated risk of MPN. This research highlights a significant association between various immune cell phenotypes and the risk of developing MPN, thereby advancing our understanding of the intricate interplay between immune cell traits and the progression of MPN.