As a result of its severe immunosuppressive nature, CIAV persists as a critical pathogen causing substantial economic concerns in global poultry production. The emergence of genetic variants and reports of suspected vaccine sub-optimal protection in Egyptian broiler flocks necessitates an urgent investigation of currently circulating strains. In this study, 165 samples were collected from six Egyptian governorates (2024–2025). PCR screening revealed 38 positive cases, and six isolates were selected for full-length sequencing of the VP1 and VP2 genes. Molecular analysis identified the isolates as Genotype II, showing significant genetic drift from Genotype I vaccinal strains. Key nonsynonymous mutations, notably H22Q in VP1, suggested potential antigenic escape, while the VP2 gene maintained 100% amino acid identity despite multiple silent mutations. Experimentally, the Genotype II isolate exhibited extreme …