Previous observations suggested that there may be an association between elevated serum copper (Cu) levels and post-partum depression (PPD). In this study, we examined Zn and Cu levels in women with completed pregnancies who had a history of PPD and compared them to women who did not have depression, and to women who reported having been depressed, but without a history of PPD. Cu levels were significantly higher in women having a history of PPD compared both to non-depressed women and to depressed women without a history of PPD. The mean serum Cu level of 78 women with a history of PPD was 131+/-39microg/dL compared with 111+/-25microg/dL in 148 women without such a history, and 106+/-20microg/dL in non-depressed controls (p<0.001). Zn levels did not differ across the three groups. Cu/Zn ratios were significantly higher in the PPD-history-positive group, due to the significant differences in Cu levels. Cu and Zn levels were not significantly different in depressed and non-depressed men, nor between non-depressed women and non-depressed men. Depressed women had higher Cu, but not Zn, levels compared with men. The nature of the association between elevated Cu values and PPD is, as yet, unknown; however Cu has roles in a variety of physiological systems that may be implicated in the development of PPD.