Chronic stress is a known risk factor for breast cancer, yet the underlying mechanisms are unclear. This study explores the potential involvement of microbial and metabolic signals in chronic stress-promoted breast cancer progression, revealing that reduced abundances of Blautia and its metabolite acetate may contribute to this process. Treatment with Blautia and acetate increases antitumor responses of CD8 T cells and reverses stress-promoted breast cancer progression in female mice. Patients with depression exhibit lower abundances of Blautia and acetate, and breast cancer female patients with depression display lower abundances of acetate, decreased numbers of tumor-infiltrating CD8 T cells, and an increased risk of metastasis. These results suggest that Blautia-derived acetate plays a crucial role in modulating the immune response to breast cancer, and its reduction may contribute to chronic stress-promoted cancer progression. Our findings advance the understanding of microbial and metabolic signals implicated in cancer in patients with depression and may provide therapeutic options for female patients with breast cancer and depression.