Copper chaperone for Cu, Zn superoxide dismutase (CCS) has been shown to be reflective of Cu status in mice and rats. The objective of this study was to evaluate liver and erythrocyte CCS as an indicator of Cu status in beef cattle (Exp. 1), and to test the acute-phase properties of CCS under conditions of inflammation (Exp. 2). In Exp. 1, samples of whole blood and liver were collected at slaughter (492 d of age) from 15 Cu-deficient and 6 Cu-adequate Angus calves. At the time of tissue collection, severe Cu deficiency had been achieved and differences (P < 0.0001) in plasma and liver Cu among Cu-adequate and Cu-deficient calves were extreme (1.26 vs. 0.19 mg/L and 208.4 vs. 6.3 mg/kg for plasma and liver Cu, respectively). Protein levels of CCS were greater in liver (40%; P = 0.02) and erythrocytes (65%; P < 0.0001) of Cu-deficient vs. Cu-adequate calves. In Exp. 2, inflammatory responses were elicited in beef heifers by administration of a Mannheimia hemolytica vaccine. Four days after vaccination, plasma concentrations of the Cu-dependent protein ceruloplasmin and the Cu-independent protein haptoglobin were increased (P < 0.001) by 71 and 83%, respectively. In contrast, detection of CCS protein in samples of liver and erythrocytes did not differ (P >or= 0.45) between baseline (d 0) and d 4 after vaccination. These data demonstrate that bovine erythrocyte and liver CCS protein levels increase in Cu-deficient cattle. Furthermore, levels of CCS protein do not change after a vaccine-induced inflammatory response, suggesting that unlike ceruloplasmin, CCS may be a reliable indicator of Cu status in cattle.