We performed single-cell proteome/transcriptome co-profiling in GV and MII-aged oocytes from mice and humans, revealing species- and stage-specific proteomic/transcriptomic changes during oocyte aging. Strikingly, we observed uncoupled proteomic and transcriptomic alterations, indicating that proteomic changes in aged oocytes are not primarily driven by RNA alterations. Leveraging our single-cell profiling, we identified molecular features underlying quality heterogeneity in aged oocytes and revealed MCT4 as a conserved oocyte aging biomarker.