There is little objective data on how cancer and its therapy affect physical activity. The main aims of this pilot study were 1) to compare physical activity in patients receiving palliative chemotherapy and healthy controls, and 2) to explore the relationship between patients' activity, quality of life (QoL), and clinical performance status. A miniaturized electronic meter objectively recorded activity for one week in 20 patients with upper gastrointestinal cancer receiving palliative chemotherapy and in 13 age-matched healthy controls. Patients also completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; fatigue), and Functional Assessment of Anorexia and Cachexia Therapy (FAACT; anorexia/cachexia) quality-of-life questionnaires. The patients' median estimated total energy expenditure was 8% lower (P = 0.0003), median time spent upright was approximately two hours/day less (P = 0.0002), and median steps taken/day was 43% lower (P = 0.002) than that of the control group. Neither estimated energy expenditure nor average steps taken/day correlated significantly with EORTC QLQ-C30 physical functioning, fatigue, or global health status/QoL. There was no correlation with the FAACT "Trial Outcome Index" (TOI), but the FACIT-F TOI and both estimated energy expenditure and the average steps taken/day correlated significantly (r = 0.59, P = 0.009 and r = 0.59, P = 0.008). It is concluded that patients receiving palliative chemotherapy were less active than healthy controls; however, the relationship between physical activity and QoL requires further characterization.