In this study we investigated the relationship between health-related quality of life, fatigue, and activity levels of people with anemia secondary to chronic kidney disease over a 12 month period following the introduction of an erythropoietin-stimulating agent. Using a longitudinal repeated-measure design, 28 people with chronic kidney disease completed the Short Form-36 Health Survey, Human Activity Profile and Fatigue Severity Scale at the commencement of an erythropoietin-stimulating agent, and then at 3, 6, and 12 months. Over a 12 month period, a significant change was found for health-related quality of life in relation to role-physical, vitality, mental health/emotional well-being, and overall mental health. However, activity levels did not significantly improve during that time. Renal nurses in dialysis units and chronic kidney disease outpatient clinics have repeated and frequent contact with people with chronic kidney disease over long periods of time, and are in an ideal position to routinely assess fatigue and activity levels and to institute timely interventions to optimize health-related quality of life and independent activity.