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The tumor microenvironment has recently emerged as a critical component of high-grade serous ovarian cancer (HGSC) disease progression. Specifically, cancer-associated fibroblasts (CAFs) have been recognized as key players in various pro-oncogenic processes. Here, we use mass-spectrometry (MS) to characterize the proteomes of HGSC patient-derived CAFs and compare them to those of the epithelial component of HGSC to gain a deeper understanding into their tumor-promoting phenotype. We integrate our data with primary tissue data to define a proteomic signature of HGSC CAFs and uncover multiple novel CAF proteins that are prognostic in an independent HGSC patient cohort. Our data represent the first MS-based global proteomic characterization of CAFs in HGSC and further highlights the clinical significance of HGSC CAFs.