Simple SummaryMannheimia haemolyticais a key contributor to bovine respiratory disease (BRD) in cattle. It is commonly found in calves and young cattle with enzootic pneumonia. Traditional visual assessments for BRD can be unreliable, leading to improper treatment and disease spread. The indirect ELISAs described in this study detect specificM. haemolytica-IgG, IgM, and IgA, and have demonstrated high diagnostic sensitivity and specificity. These tests can be used for disease surveillance and prevention in feedlot cattle.AbstractMannheimia haemolyticais one of the major causes of bovine respiratory disease in cattle. The organism is the primary bacterium isolated from calves and young cattle affected with enzootic pneumonia. Novel indirect ELISAs were developed and evaluated to enable quantification of antibody responses to whole cell antigens usingM. haemolyticaA1 strain P1148. In this study, the ELISAs were initially developed using sera from bothM. haemolytica-culture-free and clinically infected cattle, then the final prototypes were tested in the validation phase using a larger set of known-statusM. haemolyticasera (n= 145) collected from feedlot cattle. The test showed good inter-assay and intra-assay repeatability. Diagnostic sensitivity and specificity were estimated at 91% and 87% for IgG at a cutoff of S/P ≥ 0.8. IgM diagnostic sensitivity and specificity were 91% and 81% at a cutoff of sample to positive (S/P) ratio ≥ 0.8. IgA diagnostic sensitivity was 89% whereas specificity was 78% at a cutoff of S/P ≥ 0.2. ELISA results of all isotypes were related to the diagnosis of respiratory disease and isolation ofM. haemolytica(p-value < 0.05). These data suggest thatM. haemolyticaELISAs can be adapted to the detection and quantification of antibody in serum specimens and support the use of these tests for the disease surveillance and disease prevention research in feedlot cattle.