To examine the patterns of fatigue, physical activity, health status, and quality of life before and after high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT) and to examine the feasibility of obtaining real-time fatigue and physical activity data. Prospective, repeated measures. Two midwestern academic medical centers. Convenience sample of autologous or allogeneic patients undergoing HSCT (N = 20 baseline, N = 17 post-transplant). Subjects were assessed over a five-day period before and after HSCT for a total of 10 days. Subjects rated fatigue intensity three times daily and wore a wrist actigraph to measure physical activity. At the end of both five-day periods, subjects completed measures of perceived health status (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) and life satisfaction Quality of Life Index). Fatigue, physical activity, perceived health status, and quality of life. Study results indicate that fatigue significantly increased and physical activity decreased following high-dose chemotherapy and HSCT. The decline coincided with diminished physical, emotional, role, and cognitive functioning. The symptoms that patients experienced (i.e., fatigue, pain, nausea and vomiting, sleep disturbances, appetite loss, and diarrhea) increased during the acute post-transplant period. No significant changes in life satisfaction were found. The study findings suggest that patients receiving high-dose chemotherapy followed by HSCT experience increased fatigue, reduced physical activity, diminished functioning, and poorer quality of life immediately after transplant. Findings demonstrate that real-time fatigue and physical activity data can feasibly be collected in acutely ill patients. Patients undergoing HSCT require considerable supportive nursing care immediately following transplant. Clinicians and researchers need to strive for effective symptom management to improve the likelihood of successful outcomes.