Background: Thyroid hormone metabolism is modulated by starvation and overfeeding but also by dietary composition. Unfortunately, little is known about the effect of malnutrition on disease-induced nonthyroidal illness (NTI). In this study, we investigated whether the degree of NTI after surgery differed between severely malnourished and well-fed patients with head and neck cancer. Methods: Plasma levels of the thyroid hormones 3',5-triiodothyronine (T 3), reverse T3 (rT3), free T4 (FT4), and thyrotropin (TSH) were measured on the first day before the operation and on the first, fourth, and seventh day after the operation in 16 malnourished patients who were admitted for intentional curative surgery of T1-T4 carcinomas of the head and neck. Six well-fed head and neck cancer patients eligible for surgical treatment served as a control group. Results: In the malnourished group, rT3 showed a significant increase, whereas T3and FT4 decreased significantly due to the operation. TSH showed no significant change. During the postoperative course, it took 7 days until rT3 and 4 days until T3 and FT4were restored to their preoperative value. In contrast, well-fed patients did not develop NTI. Conclusions: This study shows that peri- and postoperative rT 3, T3, and FT4 levels change significantly in malnourished patients compared with well-fed patients. Therefore, it can be concluded that nutrition status of patients undergoing major head and neck surgery should be optimized in order to prevent the development of NTI.