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Most cases and deaths from ovarian cancer are associated with high\u2010grade serous ovarian carcinoma (HGSOC). We immunohistochemically analyzed the histological subtypes of ovarian cancer (high\u2010grade serous, low\u2010grade serous, clear cell, mucinous, and endometrioid) for nerves; only HGSOCs were densely innervated. We previously defined that tumor\u2010released small extracellular vesicles (sEVs) recruit nerves to the tumor bed and thus tested whether the difference in nerve infiltration amongst ovarian cancers was associated with sEVs. Using an in vitro neurite outgrowth assay, we found that HGSOC sEVs harbored robust neurite outgrowth activity. Importantly, sEVs from fallopian tube cell lines (the primary cell of origin of HGSOC) predominantly lacked this activity. Implantation of a syngeneic mouse model of HGSOC into transgenic mice lacking tumor\u2010infiltrating nerves slowed tumor growth, sensitized disease to carboplatin, and improved survival. 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