The aim of this study was to examine the relationship of changes in hemoglobin levels to changes in fatigue and cognitive functioning in cancer patients undergoing chemotherapy treatment. Seventy-seven (77) patients completed a self-administered measure of fatigue and a battery of psychometrician-administered measures of cognitive performance before the start of chemotherapy and again before the start of the fourth treatment cycle. Hemoglobin levels were measured at corresponding timepoints. Findings partially supported the hypothesis that greater declines in hemoglobin over the course of repeated chemotherapy administrations would be accompanied by greater increases in fatigue and greater declines in cognitive performance over the same interval. Among the subset of 49 patients who demonstrated a decline in hemoglobin to a final value < or =12 g/dL, greater declines in hemoglobin were significantly (P<0.05) related to greater increases in fatigue duration and disruptiveness and more negative changes in performance on three cognitive tasks. These findings suggest that, in addition to previously reported relationships with fatigue, declines in hemoglobin levels during chemotherapy treatment are associated with adverse changes in cognitive functioning.