Betanoda virus is an emerging problem in several marine fish species in various geographic areas all over the world. In recent years, mullets stock of the Caspian Sea decreased dramatically and a betanoda virus likeagent was introduced as the cause of mullet's mortality. The main objective of the present study is to compare hemato-biochemical parameters in healthy and infected sharpnose mullets (Liza saliens) to betanoda virus likeagent. The adult sharpnose mullets (34 clinically affected fish ? 34 apparently healthy fish) were captured from the southeast the Caspian Sea from 2012 to 2013. All of the captured fish were 4 or 5 years old. The main clinical sings of infected fish were lethargy, severe abdominal distention, abnormal swimming and hyperinflation of swim bladder. The results showed that the weight and total length of infected fish were significantly lower than the healthy fish. The results of histopatological evaluation and indirect florescent antibody test were confirmed the presence of a betanoda virus-like agent in infected fish. The diseased fish were severely anemic (hypochromic macrocytic anemia) and had a serious haemopoietic disorders. The anemia associated with a sever leukopenia, a significant rise of neutrophils and immature neutrophils and a significant decries of lymphocytes percentage. Total protein, albumin and total immunoglobulin levels were significantly reduced in the serum of infected fish, while the activities of aspartate aminotransferase and alanine aminotransferase significantly increased when compared to the healthy fish. These results suggested that the feeding of the infected fish to betanoda virus like-agent were disturbed and it could be cause haemato-biochemical disorder and mortality of the fish in Iranian water of the Caspian Sea.