Carotenoids are unstable and susceptible to disruption by environmental factors such as heat, light, and solvents. However, there is little information on the effect of metal ions on stability of carotenoids, especially those essential elements in human nutrition. Astaxanthin is one of the few carotenoids containing four oxygen donors. Usually, these oxygen donors can coordinate with heavy metal ions such as Cu(II) and Fe(III). In the present study, the interaction of trans-astaxanthin with Cu(II) was examined. It was found that Cu(II) markedly induces the conversion of trans-astaxanthin to its cis forms, which mainly consist of 9-cis-astaxanthin and 13-cis-astaxanthin as suggested by UV-visible spectra and HPLC measurements. Increasing either incubation time of Cu(II) and trans-astaxanthin in ethanol or the Cu(II)/astaxanthin ratio results in an increased percentage of cis isomers derived from trans-astaxanthin. All these results provide important information on the effects of dietary factors on the bioavailability and bioactivity of trans-astaxanthin.