An epidemic that mainly endangered 3–7-day-old piglets struck many farms in Shandong Province, China in 2013 and caused heavy losses. To identify the pathogenesis, the type of lesions, and the causative agent, systemic examinations were performed. Autopsy showed multiple lesions, including necrotic foci of the spleen and liver, punctate hemorrhage of the renal cortex, and interstitial pneumonia. Histological examinations showed typical nonsuppurative encephalitis, necrotic lymphocytes, and reticuloendothelial cells in lymphatic tissues, as well as eosinophilic inclusion bodies in the nuclei of reticuloendothelial cells, necrotic foci in liver cells, and hemorrhagic glomeruli. The average seroprevalence rate of field pseudorabies virus (PRV; Suid herpesvirus 1) of a representative farm tested by enzyme-linked immunosorbent assay was 46%, indicating that the PRV infectious pressure was quite severe especially among gilts, young multiparous sows, boars, and growing–finishing pigs. The glycoprotein E (gE) gene of PRV was detected in 8 of 10 clinical samples, and the virus in the positive samples induced obvious cytopathic effects. An immunoperoxidase monolayer assay showed that PRV antigens were distributed both in the nucleoli and cytoplasm of infected cells. Sequencing and phylogenetic analysis of the gE gene showed that the strain isolated herein, TaiAn SD 2013, was highly similar to previously isolated strains, especially those isolated in northern China in 2013, and was closely related to other isolates from Asia. Evidence confirmed that the variant PRV was the etiologic agent of this epidemic, suggesting that the Bartha-K61 vaccine does not provide complete protection against PRV infection. Further challenge tests are ongoing to investigate the virulence of variant PRV.