Small extracellular vesicles (sEVs), lipid-bilayer delimited particles (50-200 nm) released by cells, are considered a new class of liquid biopsy biomarkers for stealth cancers, e.g., HGSOC. HGSOC originates from the fallopian tube (FT) and progresses from p53 signatures to a precursor lesion called serous tubal intraepithelial carcinoma (STIC). We hypothesize that sEVs play a role in ovarian pathogenesis, carry cargo reflective of the site of origin, and are biomarkers for early detection. To advance this idea, we established a case-control study cohort of archival plasma samples from 30 HGSOC patients (10 early-stage and 20 late-stage) and 40 healthy controls. sEVs were isolated using size exclusion chromatography, and proteomic profiles were established using mass spectrometry (LC-MS/MS). 1,078 EV proteins (exo-proteins) were identified across all samples, with 52 upregulated exo-proteins in early-stage HGSOC, and 59 upregulated exo-proteins in late-stage HGSOC (logFC>1, p<0.05). Upregulated exo-proteins were prioritized based on FT origin and tissue expression in STIC lesions. Seven candidate exo-proteins were validated by immunohistochemistry in FT with STIC lesions and HGSOC tissues and by western blot in FT/HGSOC cell-derived EVs. In summary, our EV proteomics using early-stage HGSOC clinical samples uncovered exo-biomarkers for early detection; potentially while still confined to the FT.