It is well known that weight loss occurs in patients with chronic graft-versus-host disease. However, the severity and frequency of weight loss in this population have not been adequately described. Recent data suggest that a body-mass index (BMI) below 21.9 is an independent risk factor for mortality. In our analysis we have shown that out of 93 patients with cGVHD, 43% are malnourished as evidenced by a BMI less than 21.9 and 14% are severely malnourished (BMI less than 18.5). In addition, there is a clear trend showing that patients with active, ongoing cGVHD have lower BMIs (P = 0.02). Furthermore, we show that many symptoms thought to contribute to weight loss in patients with cGVHD, such as odynophagia and oral sensitivity, are not related to weight loss in our population. We conclude that, in all likelihood, unknown causes still exist that are responsible for weight loss in this group of patients. Elevated resting energy expenditure and elevated serum tumor necrosis factor-alpha are potential contributors to weight loss that will be tested in future studies. We also conclude that treating cGVHD aggressively may help reverse weight loss and malnutrition, which may be independent risk factors for mortality in this population.