Highly pathogenic avian influenza virus (HPAIV) poses threats to animal and human health worldwide. A common kestrel(Falco tinnunculus) was submitted to Avian and Rabbit Medicine Department, Zagazig University, Egypt. It exhibited torticollis, incoordination, and inability to stand. Conjunctivitis and crust formation were seen. Postmortem findings revealed congestion in internal organs and greenish content in gizzard. No avian pox virus was detected in cutaneous lesions neither in histopathological sections nor in PCR. The presence of HPAIV H5N1 was confirmed by both virus isolation and RT-PCR. The mean death time of virus in chicken embryo is 36.2 hours. Influenza A virus antigen was detected in renal glomerular tufts and neurons of the submucosal plexus of the intestine of falcon by IHC. This paper describes the isolation of HPAIV H5N1 in falcon with systemic infection suggests that common kestrel falcon can be susceptible to HPAIV and could be a source of infection to other birds and human.