The threat of the spread of small ruminant plague to livestock in a number of countries makes the study of the mechanisms of development and prevention of this disease a priority area of research. Therefore, the purpose of the study was to investigate the changes in the blood system and organs of the immune system in small ruminant plague, which led to the development of immunodeficiency in the body of infected animals. Haematological and histological methods were used in the study. As a result of the work carried out, a decrease in the total number of leukocytes in the peripheral blood from 12.4 to 7.3×109/l was detected in 3 sheep that died from small ruminant plague. There was also a shift in the normal ratio of granulocytes to agranulocytes from 1:1 to 2.5:1 towards granulocytes, which was provoked by a sharp decrease in the number of lymphocytes from 49% to 25% in the leukocyte blood count. Such changes in the blood system were provoked by significant degenerative changes in the lymphoid tissue of immunocompetent organs – lymph nodes and spleen. Histological examination of the parenchyma of the above organs revealed atrophy of T- and B-dependent zones and apoptosis of lymphocytes. Taken together, these signs – haematological and histological – allow for the conclusion that both the humoral and cellular immune response systems in the body are reduced. In the affected areas of the lungs, an inflammatory reaction is observed with active migration of neutrophils and macrophages to the inflammation zone. But the active multiplication of the virus in the lung cells indicates a lack of immunity. Thus, the study revealed the mechanisms of the development of humoral and cellular immunodeficiency in small ruminant plague (SRP), which would allow developing more effective methods of combating this disease