Chemotherapy for breast cancer leads to increased fatigue, poor mood, and reduced quality of life. Few studies have examined possible changes in inflammation during chemotherapy as potential contributors to this phenomenon. This study examined the relationship among circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) and fatigue, depressed mood, and quality of life before and during anthracycline-based chemotherapy. Twenty-nine women diagnosed with stage I-IIIA breast cancer (mean age 49.5 years, S.D.+/-11) were studied prior to cycle 1 of chemotherapy and 2.5 months later at the start of cycle 4 of chemotherapy. Chemotherapy led to a significant increase in sICAM-1 (P<0.05) and VEGF (P<0.01) levels, as well as increased ratings of fatigue (P<0.01), depressed mood (P<0.03), and poorer quality of life (P<0.01). Multiple regression analyses revealed that elevated VEGF (P<0.01) and sICAM-1 (P<0.02) were related to the increased fatigue and/or poorer quality of life as a result of chemotherapy. Pre-chemotherapy levels of VEGF and pre-chemotherapy ratings of quality of life predicted quality of life in response to chemotherapy (P<0.001). The findings contribute to the literature by showing that both pre-chemotherapy and chemotherapy-induced changes in inflammation are related to changes in fatigue and quality of life in response to chemotherapy.