Copper (Cu) status is often judged by the plasma level of its chief transport protein, ceruloplasmin (Cp). Only copper deficiency and heredity are known to decrease circulating Cp. Cp is an acute-phase responsive protein in trauma and it is also induced by Cu supplementation. Despite this, plasma concentrations of Cp remain low during the acute recovery from major burn injury. The high provision of vitamin C typically used in burn patients may influence these observations when an indirect oxidase activity assay is used. We employed a radial immunodiffusion (RID) assay specific for the Cp protein as well as an indirect oxidase assay for Cp in a series of 11 burned children who were supplemented with both Cu and vitamin C, either enterally or parenterally. Our findings confirm that low Cp is a characteristic of the acute recovery from major burns. The oxidase assay is shown to be valid for very low Cp levels even during high vitamin C provision. When these data are combined with our previously reported series, a strong relationship between the size of the open wound area and the amount of circulating Cp is demonstrated. Copper supplementation by either the enteral or parenteral routes is only marginally successful in restoring Cp toward normal levels.