The objective of this double-blind, randomized study was to establish whether sodium selenite administered orally or intravenously reduces postoperative lymphedema after oral tumor surgery and to study the effect of sodium selenite on glutathione peroxidase (GPX) activity and oxygen radical production. Twenty patients were enrolled in the study. Each of the participants received 1,000 microg sodium selenite intravenously or orally daily for 3 wk during the pre-, intra-, and postoperative period. The extent of lymphedema was measured for 2 wk and the plasma and whole-blood selenium concentration, GPX, reactive oxygen species (ROS), NO, and malonic dialdehyde were measured for 1 yr postoperatively. There was an inverse correlation between the severity of the lymphedema and the whole-blood/plasma selenium concentration and GPX activity. In addition, a positive correlation between the ROS concentration and the extent of lymphedema was observed. A significant reduction of lymphedema occurred in the sodium selenite-treated group. It is concluded that sodium selenite represents a suitable adjuvant treatment of secondary lymphedema in surgically treated patients with tumors in the oral and maxillofacial areas. Treatment with sodium selenite is especially advantageous as it can be instituted immediately after surgery prior to wound healing when manual lymphatic decongestion therapy cannot be applied.