Interaction of taste molecules with saliva is the first step in the flavor perception process. Saliva is assumed to influence copper-induced sensation by controlling the copper solubility or causing astringency via binding of proteins with copper. This study was performed to identify the nature of copper-protein interactions in relation to the sensory perception of copper. Saliva was treated with CuSO4 · 5H2O at levels of 0, 2.5, 5, 10, 20, or 40 mg/L, and changes in salivary proteins were analyzed using high performance liquid chromatography (HPLC) and sodium dodecyl sulfate- polyacrylamide gel electrophoresis (SDS-PAGE). Protein peaks that showed changes in HPLC were characterized with SDS-PAGE. HPLC analysis revealed that copper treatment up to 40 mg/L decreased several proteins, including the dominant peak, by 70%. This peak was composed of α-amylase, a secretory component, and basic proline-rich proteins. SDS-PAGE results showed that salivary proteins of molecular weight 29 kDa and 33 kDa precipitated when copper was added at concentrations ≥10 mg/L. This study provides biochemical information for understanding perception mechanisms of copper sensation.