The MITO-END3 trial compared carboplatin and paclitaxel (CP) with avelumab plus carboplatin and paclitaxel (CPA) as first-line treatment in endometrial cancer (EC) patients and demonstrated a significant interaction between avelumab response and mismatch repair status. To investigate prognostic/predictive biomarker, twenty-nine MITO-END3-EC patients were evaluated at pre-treatment (B1) and at the end of CP/CPA treatment (B2) for peripheral Myeloid derived suppressor cells (MDSC) and Tregs. At B2, effector Tregs frequency was significantly higher in patients treated with CPA as compared to CP (p=0.038). Both treatments (CP/CPA) induced significant decrease in peripheral M-MDSC (-5.41%) in TCGA 2-MSI-High as compared to TCGA-category 4 tumors (p=0.004). In accordance, both treatments induced M-MDSCs (+5.34%) in MSS patients as compared to MSI-High patients (p=0.001). Moreover, in a subgroup of patients, primary tumors were highly infiltrated by M-MDSCs in MSS as compared to MSI-high ECs. A post hoc analysis displayed higher frequeny of M-MDSCs (p=0.020) and lower frequency of CD4+ (p<0.005) at pretreatment in EC patients as compared to healthy donors. In conclusion, the peripheral evaluation of MDSCs and Tregs correlated with molecular features in EC treated with CP/CPA and may add insights in identifying EC patients responder to first line chemo/chemo-immunotherapy.