Neoadjuvant chemotherapy (NACT) influences the anticancer response by favourably altering the immune microenvironment. However, the effects of NACT on peripheral monocytes and their prognostic contribution to the NACT response have not yet been clarified. We aimed to evaluate the potential therapeutic responses and possible predictive value of double-positive (CD14 + CD16 +) monocytes and soluble CD163 (sCD163) in Egyptian breast cancer patients. Blood samples were obtained before and after neoadjuvant therapy from 30 patients with invasive breast cancer, and the expression of CD14 and CD16 was assessed via flow cytometry. The patients' sCD163 levels were also determined in both the serum and culture supernatant using enzyme-linked immunosorbent assay (ELISA). The results revealed that NACT was associated with a significant decrease in double-positive monocytes and sCD163 levels. In addition, both double-positive monocytes and serum sCD163 were significantly associated with a partial clinical response. Double-positive monocytes and serum sCD163 levels may be related to therapeutic response, suggesting their possible predictive value in breast cancer patients receiving NACT.