Highly pathogenic influenza virus (HPAIV) H5N1 has caused mortality and morbidity in many species of domestic and wild bird. The Houbara bustard (Chlamydotis undulata macqueenii) is a solitary bird that inhabits semi-desert regions. It is known to be susceptible to avianpox, avian paramyxovirus type 1, and low-pathogenicity avian influenza H9N2. We report an outbreak of H5N1 HPAIV in Houbara bustards, which were introduced into the Kingdom of Saudi Arabia for falconry purposes. Ninety-three per cent mortality (38 out of 41 birds) in the infected Houbara bustard flock and about 62.5% mortality (10 out of 16 birds) in falcons that came in contact with these birds were observed. Pooled cloacal and tracheal swabs from Houbara bustards as well as visceral organ homogenates collected in Houbara bustards and falcons were tested by real-time reverse transcriptase-polymerase chain reaction, and virus isolation was attempted in specific pathogen free hens' eggs. The viruses isolated were characterized as HPAIV H5N1. Phylogenetic analysis of the haemagglutinating and Neuraminidase (NA) genes revealed that the viruses isolated from Houbara bustards and falcons were closely related to each other and to Kuwaiti H5N1 strains isolated in 2007. Interestingly, they were genetically distinguishable from the co-circulating A/H5N1 viruses in Kingdom of Saudi Arabia causing outbreaks in domestic birds. This case emphasizes the need for surveillance of this endangered species in its natural habitat.