Breast cancer (BC) poses a global health challenge, necessitating accessible prognostic biomarkers. Systemic inflammatory markers from complete blood counts, such as neutrophil-to-lymphocyte ratio (NLR) and red cell index (RCI), have shown prognostic potential. This retrospective study evaluated the prognostic significance of pre-treatment NLR and RCI for overall survival (OS) in 144 Jordanian BC patients (KAUH, 2011–2025) undergoing chemotherapy. Kaplan-Meier analysis revealed that high pre-treatment NLR (≥ 4.25) and high RCI (≥ 0.02) were significantly associated with shorter OS. Multivariate Cox regression identified elevated pre-treatment RCI (≥ 0.02) and metastasis at diagnosis as independent predictors of increased mortality and worse OS. A significant association between high NLR and RCI values was also observed, suggesting a link between systemic inflammation and erythrocytic dysregulation. In conclusion, pre-treatment RCI and metastasis are strong independent predictors of OS in this cohort, with RCI demonstrating substantial prognostic value.