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To examine the relationships among fatigue and physical and mental quality of life (QOL) and different adjuvant chemotherapy regimens in patients with stage I-IIIA breast cancer prior to, during, and after treatment.Longitudinal, descriptive design embedded in a randomized, clinical trial.Outpatient oncology clinics in the midwestern United States.196 postoperative women, mean age of 52 years, receiving anthracycline-based chemotherapy regimens: dose-dense taxane, dose-standard taxane, or dose-standard without taxane.The Piper Fatigue Scale and Medical Outcomes Study SF-36® (v.2) Survey were completed 48 hours prior to treatment 1, at treatments 4 and 8, and 30 days after the final treatment.Fatigue, adjuvant chemotherapy regimen, and QOL.Fatigue and mental QOL changed significantly over time for all regimens, but the patterns of change did not differ based on regimen. Physical QOL changed significantly over time for all regimens, and the pattern of change differed based on whether taxanes were received. Higher fatigue was correlated with lower physical and mental QOL prior to and 30 days after the final treatment, regardless of regimen.Women who receive taxanes are at higher risk for lower physical QOL over time. Higher fatigue was associated with lower QOL regardless of the chemotherapy regimens.Clinicians should screen patients for fatigue and assess for contributing factors at clinic visits. Methods to integrate evidence-based fatigue interventions into practice should be tested and outcomes evaluated.