Highly pathogenic avian influenza (HPAI) viruses, particularly those with a H5 subtype arise from poultry and can cause severe morbidity and mortality in humans. We have undertaken an investigation into the chicken immune response to HPAI infection and looked at correlations of chicken haplotype with disease outcome. In one H5 subtype infection caused 100 % mortality in all birds within 30-48 hours of inoculation, with clinical signs including facial swelling, depression, hunching and fluffed feathers. High virus titers were observed at necropsy in blood and all tissues, indicating systemic infection. Pro-inflammatory cytokines were greatly elevated and interestingly, we showed a significant decrease in the proportion of CD8 T cell corresponding to HPAI infection.