Update information. Obstetric Antiphospholipid syndrome (OAPS) is a multisystem disorder characterized by thrombosis and/or recurrent fetal loss. In this study, we aim to further explore the pathological mechanism of OAPS. Herein, we carried out quantitative proteomic analysis of serum samples from OAPS patients and healthy controls to identify differentially expressed proteins between them. A data-independent Acquisition (DIA) mass spectrometry method for unbiased proteome profiling for the high sensitivity detection of clinical microsamples. A set of 93 proteins were differentially identified, including 75 up-regulated and 18 down-regulated proteins compared with the levels in controls. GO enrichment analysis showed that most of the differentially expressed proteins were located in extracellular region part, extracellular region and extracellular space, mainly involved in in biological processes such as response to chemical, response to organic substance and cellular response to chemical stimulus, and the main molecular functions are protein binding, receptor binding and identical protein binding. The most enriched KEGG pathways were autoimmune diseases and allergic diseases pathway, metabolic related pathways, pathogen infection pathways, and lysosome pathways. There were key nodes among the differentially expressed proteins including HLA-DRA,CRP and TNFSF13B. Our study formed a basis to perform new proteomic studies in OAPS to better understand the proteins involved in the pathogenesis of the syndrome and to provides the possibility to explore the pathogenesis of OAPS.