Mass mortality in Caspian terns (Hydroprogne caspia), Pallas’s gulls (Ichthyaetus ichthyaetus), and Caspian gulls (Larus cachinnans) was recorded on the northeastern shores of the Caspian Sea in June 2022. More than 5000 gulls and terns died due to the outbreak. The outbreak was investigated in the field, and representative numbers of samples were collected and analyzed using pathological, virological, and molecular methods. Highly pathogenic avian influenza A (H5N1) viruses were detected and isolated from samples collected from dead birds. Genetic and phylogenetic analyses indicated that the hemagglutinin (HA) genes belonged to the clade 2.3.4.4.b of the H5Nx HPAI viruses, B2 sub-lineage, and were closely related to the highly pathogenic influenza viruses, caused an outbreak in wild birds with a high mortality rate in the western part of the Caspian Sea.