Preterm birth (PTB) is a major problem affecting perinatal health, directly increasing the mortality risk of mother and infant that often results from the breakdown of the maternal- fetal immune balance. Increasing evidence shows the essential role of mucosal-associated invariant T (MAIT) cells to balance antibacterial function and immune tolerance function during pregnancy. However, the phenotype and function of placental MAIT cells and their specific mechanisms in PTB remain unclear. Here, we report that MAIT cells in the placenta of PTB show increased activation levels and decreased IFN-γ secretion capacity compared with those in normal pregnancy. Moreover, our data indicate gravidity is a factor affecting placental MAIT cells during pregnancies. Multi-omics analysis indicated aberrant immune activation and abnormal increase of lipids and lipid-like metabolites in the placental microenvironment of PTB. Moreover, the proportion and activation of MAIT cells were positively correlated with the abnormal increase of lipids and lipid-like metabolites. Together, our work revealed that abnormal activation and impaired function of MAIT cells may be related to abnormal elevation of lipids and lipid-like metabolites in PTB.© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.