This study presents a cell-type–resolved quantitative proteomics analysis of paired primary and recurrent ascites samples from patients with high-grade serous ovarian carcinoma (HGSOC). Ascites samples were collected from three patients (IROC60, IROC65, and IROC126) at diagnosis and upon disease recurrence following platinum–taxane chemotherapy. For each sample, ascites-derived cells were fractionated into unsorted, CD45⁻ (tumor-enriched), and CD45⁺ (immune-enriched) populations using magnetic-activated cell sorting. Using label-free LC–MS/MS proteomics, we quantified proteome-wide changes associated with disease recurrence across distinct cellular compartments. Pathway-level analyses revealed consistent suppression of interferon signaling across tumor and immune fractions, alongside enhanced oxidative phosphorylation and metabolic reprogramming in recurrent tumor cells. Immune-enriched fractions exhibited signatures of immunosuppression, including reduced antigen presentation and enrichment of regulatory and monocyte-related pathways. Together, this dataset provides a comprehensive proteomic resource for investigating tumor–immune interactions and recurrence-associated molecular remodeling within the ovarian cancer ascites microenvironment.