In the present study, the pathogenic mechanism of white spot syndrome (WSSV) in crayfish, Procambarus clarkii by investigating activities of immune cells related to innate immune function during infection was explored. White spot disease caused by WSSV leads to devastating losses in crayfish farming. Examination by transmission electron microscopy revealed abundant WSSV particles and significant changes in the different lymphoid organs of infected crayfish. WSSV infection caused parts of the gill epithelium and microvilli to be reduced in number and size or damaged, meanwhile, the mitochondria, morphology changed, with parts of the cristae diminished leaving large vacuoles. Moreover, electron dense deposits appeared and hetero-chromatinized nuclei could be seen in blood cells with ruptured nuclear membranes and outflow of nucleoplasm. Also, evident were very densely basophilic inclusions were found in interstitial hepato-pancreatic tissue, connective tissue underlying the mid gut, cardiac tissue, gill tissue and hematopoietic tissue. Transmission electron microscopy revealed the presence of previously undescribed rod-shaped, enveloped versions in the cytoplasm adjacent to the nuclei of cells from various tissues.