Liza klunzingeri is an important species in the Persian Gulf and Oman Sea. A large number of L. klunzingeri suffered acute mortality in the Persian Gulf and Oman Sea coasts. The infected fish showed some clinical signs such as abnormal and whirling swimming, changes in pigmentation, swelling of swim bladder, and belly-up position. The affected fish showed hemorrhage in lateral and abdominal cavities. Also, hemorrhages were seen in the operculum, and thoracic and caudal fins. Abdominal cavity had no abnormality. For histological examination, the samples were fixed in Bouin’s fixative. After tissue processing, 5-μm sections were stained with hematoxylin and eosin. Microscopic observation of spleen, liver, intestine, gills, and kidney tissue showed no morphological and histopathological changes. However, necrosis and vacuolation were seen in both brain and retinal tissues. Lesions were severe and widespread in the gray matter compared to white matter. The current report is the first description and account of an acute mortality with viral nervous necrosis similar clinical signs and histopathology in the Persian Gulf and Oman Sea involving L. klunzingeri.