The possibility that predators choose prey selectively based on age or condition has been suggested but rarely tested. We examined whether mountain lions (
Puma concolor
) selectively prey upon mule deer (
Odocoileus hemionus
) infected with chronic wasting disease, a prion disease. We located kill sites of mountain lions in the northern Front Range of Colorado, USA, and compared disease prevalence among lion-killed adult (≥2 years old) deer with prevalence among sympatric deer taken by hunters in the vicinity of kill sites. Hunter-killed female deer were less likely to be infected than males (odds ratios (OR) = 0.2, 95% confidence intervals (CI) = 0.1–0.6;
p
= 0.015). However, both female (OR = 8.5, 95% CI = 2.3–30.9) and male deer (OR = 3.2, 95% CI = 1–10) killed by a mountain lion were more likely to be infected than same-sex deer killed in the vicinity by a hunter (
p
< 0.001), suggesting that mountain lions in this area actively selected prion-infected individuals when targeting adult mule deer as prey items.