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Cognitive dysfunction is a potential side effect of chemotherapy, and erythropoietin might be protective. A previously reported study compared quality-of-life in women undergoing chemotherapy for breast cancer who were randomized to receive epoetin-alfa or standard care. Here, we report a non-randomized sub-study in which cognitive function of participants was evaluated at 12-30 months after chemotherapy.The primary endpoint was the proportion of women with moderate-severe cognitive impairment, as measured by the High Sensitivity Cognitive Screen (HSCS). Subjects also completed the Revised Hopkins Verbal Learning Test (HVLT-R), the Functional Assessment of Cancer Therapy—Fatigue (FACT-F) and FACT-G self-report questionnaires for fatigue and quality-of-life, and the Hospital Anxiety and Depression Scale.Of 278 patients receiving adjuvant treatment in the primary study, 87 participated in the sub-study: 45 had received epoetin-alfa and 42 standard care. Groups were well matched for age and type of chemotherapy. Eight patients (9%) had moderate-severe cognitive dysfunction by the HSCS: six of them in the epoietin-alfa group (not significant). There were no significant differences in the HVLT-R, or in fatigue, but patients who had received epoetin-alfa reported better quality-of-life.This study failed to demonstrate a protective effect of epoetin-alfa against the development of delayed cognitive dysfunction after chemotherapy.