BackgroundStress associated with changes in host immunity occurs in response to altered environmental conditions, endogenous imbalances, infectious agents and harmful stimuli. The importance of genetic diversity in chickens has increased due to individual immune differences towards resistance and susceptibility to various stimuli.ObjectivesThis study aimed to investigate the association of major histocompatibility complex (MHC) polymorphism with acute phase response (APR) in Ross 308 broiler chickens.MethodsThe allelic diversity of the LEI0258 microsatellite marker was determined in 120 Ross broilers. In addition, acute phase proteins (APPs), including serum amyloid A (SAA) and alpha‐1‐acid glycoprotein (AGP), were analysed as markers of the APR. Furthermore, leukocyte count and the heterophil/lymphocyte ratio (H/L ratio) were examined. The antibody response to the Newcastle disease vaccine (NDV) was also measured to assess humoral mediated immunity. Lastly, the correlation between immune responses and MHC alleles was investigated to identify the most effective alleles in a stress‐related situation.ResultsA total of six alleles, ranging from 195 to 448 bp, were identified. Association study revealed a significant influence of MHC alleles on APPs in Ross population (p < 0.05). Notably, Allele 448 had a significant correlation with SAA concentration and the H/L ratio. Allele 207 displayed a positive association with AGP concentration, whereas Allele 195 showed a negative association. Furthermore, a significant association was observed between Allele 448 and basopenia, as well as between Allele 195 and monocytosis.ConclusionsResults confirmed the significance of MHC as a candidate gene marker for immune responses, which supports its use for vaccine design, genetic improvement of disease‐resistant traits and resource conservation in commercial broiler chickens.