Background: Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have emerged as promising markers in assessing erythropoietin (EPO) resistance among hemodialysis (HD) patients Objective: The purpose of this study was to explore the potential of the PLR and NLR as indicators of how HD patients respond to erythropoiesis-stimulating agents (ESAs), and to see if PLR and NLR could help predict which patients might have trouble responding to ESA treatment. Patients and Methods: This was a prospective study involving 100 HD male and female patients over the age of 18 years. The patients were divided into two groups: Group I (n=47) included patients resistant to ESAs, and Group II (n=53) included patients responsive to ESAs. Results: Both PLR and NLR were inversely correlated with hemoglobin levels after three months of ESAs treatment and positively correlated with each other. PLR and NLR had nonsignificant correlations with various clinical and biochemical parameters. According to the PLR and NLR to differentiate EPO resistance in HD patients from non-EPO resistance in HD patients respectively, at a cut-off value of ≥ 44.98 and0 .835, the sensitivity was 91.5% and 89.4%, the specificity was 77.4% and 62.3%. Erythropoietin resistance index (EHRI), PLR and NLR were significantly correlated with the prediction of EPO resistance in HD patients. EHRI, PLR and NLR were significantly high between both groups. Conclusions: PLR and NLR could help in assessing both inflammation and EPO resistance in HD patients. Combining these two measures might make it easier to identify patients who need higher ESA doses.