We estimated chronic wasting disease (CWD) prevalence among vehicle-killed mule deer (Odocoileus hemionus) in select data analysis units (DAUs) in northern Colorado, USA, and compared these with estimated CWD prevalence among mule deer of the same sex sampled in the vicinity of collision sites to assess relative vulnerability of CWD-infected individuals to vehicle collisions. Twenty-five of 171 vehicle-killed mule deer tested positive for CWD (overall prevalence=0.146, 95% confidence interval [CI]=0.097–0.208); 173 of 2,317 deer sampled in the vicinity of these vehicle-killed deer tested positive (overall prevalence=0.075, 95% CI=0.064-0.085). In nine often DAU×sex comparisons, relative risk of CWD infection tended to be higher among vehicle-killed deer (range of estimated relative risks=1.6–15.9). Spongiform encephalopathy was detected in 12 of 20 (60%; 95% CI=39–81%) CWD-positive deer killed by vehicles and in 79 of 180 (44%; 95% CI=37–52%) CWD-positive deer detected via random sampling (relative risk=1.37; 95% CI=0.92–2.03), suggesting that infected deer killed by vehicles tended to be in later stages of disease than those killed by hunters. Our data offer evidence that CWD-infected mule deer may be relatively vulnerable to vehicle collisions. It follows that sampling of vehicle-killed mule deer may be exploited to increase efficiency of surveillance programs designed to detect new foci of CWD infection; moreover, evidence of increased susceptibility to vehicle collisions may aid in understanding vulnerability of CWD-infected individuals to other forms of death, particularly predation.