Bovine respiratory disease (BRD) is the primary cause of morbidity and mortality in cattle feedlots. There is a need to understand what animal health and production factors are associated with increased mortality risk due to BRD. The aim of the present study was to explore factors associated with BRD case fatality in feedlot cattle. Four pens totaling 898 steers were monitored daily for visual signs of BRD such as difficult breathing and coughing, and animals exhibiting signs of BRD were taken to the hospital shed for further examination and clinical measures. Blood samples were obtained at feedlot entry and at time of first BRD pull from animals diagnosed with BRD (n = 121) and those that died due to BRD confirmed by postmortem examination (n = 16; 13.2% case fatality rate). Mixed-effects linear regression models were used to estimate differences in animal health and production factors and the relative concentrations of 34 identified blood metabolites between animals that survived versus those that died. Generalized linear mixed-effects models were used to obtain the odds of being seronegative (at both feedlot entry and first BRD pull) to 5 BRD viruses and having a positive nasal swab result at the time of first pull in died and survived animals. Animals that died from BRD had lower average daily gain (ADG), reduced weight at first BRD pull, higher visual BRD scores and received more treatments for BRD compared with animals that survived BRD (P < 0.05). The odds of being seronegative for bovine viral diarrhea virus 1 (BVDV-1) were 5.66 times higher for animals that died compared with those that survived (P = 0.013). The odds of having a positive bovine coronavirus nasal swab result were 13.73 times higher in animals that died versus those that survived (P = 0.007). Animals that died from BRD had higher blood concentrations of α glucose chain, β-hydroxybutyrate, leucine, phenylalanine, and pyruvate compared with those that survived (P < 0.05). Animals that died from BRD had lower concentrations of acetate, citrate, and glycine compared with animals that survived (P < 0.05). The results of the current study suggest that ADG to first BRD pull, weight at first BRD pull, visual BRD score, the number of BRD treatments, seronegativity to BVDV-1, virus positive to BCoV nasal swab, and that certain blood metabolites are associated with BRD case fatality risk. The ability of these measures to predict the risk of death due to BRD needs further research.