The objective of this study is to investigate the serum beta-2-microglobulin (B2MG) and advanced oxidation protein products (AOPP) as middle molecule uremic toxins and protein carbonyl (PCO) as oxidative stress marker in uremic patients undergoing high-flux versus low-flux hemodialysis (HD) and to correlate their levels to the erythropoietin requirements for those patients. Twenty patients on chronic low-flux HD were recruited in the study. At the start of the study, all patients underwent high-flux HD for eight weeks, followed by low-flux HD for two weeks as a washout period. The patients were then subjected to another eight weeks of low-flux HD. Blood samples were obtained at the beginning and at the end of the high-flux period and the low-flux period. The mean erythropoietin dose for patients using high-flux HD was significantly lower than that for low-flux HD (P = 0.0062). Post-high flux, the B2MG and PCO levels were significantly lower than the pre-high-flux levels (P = 0.026 and 0.0005, respectively), but no significant change was observed in AOPP (P = 0.68). Post-low flux, the B2MG, AOPP and PCO were significantly higher than the pre-low-flux levels (P = 0.0002, 0.021 and <0.0001, respectively). Post-low flux, the B2MG and PCO were significantly higher than the post-high-flux levels (P <0.0001), but no significant difference was observed in AOPP (P = 0.11). High-flux HD results in reduction of some of the middle molecule toxins and PCO levels better than low-flux HD, and is associated with a better response to erythropoietin.