Technical Abstract: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) or prion disease of Rocky Mountain elk in North America. CWD is a fatal neurodegenerative disease in which the prolonged and variable incubation time is controlled in part by the host prion precursor genotype. The misfolded prion protein accumulates in brain and sometimes the lymphoid tissues of infected animals. Immunohistochemistry analysis of peripheral lymphoid tissue is used to detect elk in which the misfolded prion protein accumulates in peripheral tissue but there are no antemortem methods for assessing nervous system involvement. Recent studies have suggested that the tissue and blood levels of several minerals may be value in assessing TSE infection in sheep or cattle. The objectives of this study were to examine baseline levels of six minerals in the brain of Rocky Mountain elk with differing prion genotypes and to assess the association of mineral level with CWD infection. Elk with the long incubation genotype had significantly lower magnesium levels than elk with the short incubation time genotype. CWD positive elk had significantly lower magnesium levels than control elk. The incorporation of manganese levels in addition to magnesium significantly refined explanatory ability, even though manganese alone was not significantly associated with CWD in these samples. The study demonstrated that mineral analysis may provide an additional disease correlate for assessing CWD risk, particularly when genotype and multiple minerals are included in the analysis.