Antiphospholipid syndrome (APS) is an autoimmune disorder associated with thrombosis and adverse obstetric outcomes. Early diagnosis and intervention can improve pregnancy outcomes to some extent, but current results are unsatisfactory. Exosomes, containing biomacromolecules relevant to reproduction, play essential roles in pregnancy. However, research progress on their involvement in APS remains limited.This study aims to investigate protein profile changes in plasma exosomes and identify potential biomarkers for obstetric APS.We employed tandem mass tag (TMT) markers to analyze exosome protein profiles from 6 healthy early pregnant women and 6 early-stage APS patients. Quantitative proteomics analysis was conducted using the Maxquant search engine.Differential expression analysis identified 51 upregulated and 22 downregulated proteins in plasma exosomes from early pregnant women with APS, such as serpin peptidase inhibitor C1/A1/A7, apolipoprotein 1/2, orosomucoid 1/2 and apolipoprotein H. Kyoto Encyclopedia of Genes and Genomes analysis shows that differentially expressed proteins are enriched in the PPAR signaling pathway and staphylococcus aureus infection pathway. Enrichment analysis indicated associations with glycerolipid biosynthesis, vitamin transport, and negative regulation of very-low-density lipoprotein particle remodeling.Our study highlights alterations in the protein profiles of plasma exosomes in APS pregnant patients and proposes potential biomarkers, offering insights for early diagnosis and treatment and improving reproductive outcomes.© 2024 The Author(s).