This study was conducted to investigate the PRRS and co-infected PRRS with Hog Cholera (HC) at Bac Lieu and Soc Trang provinces from June, 2010 to June, 2011. RT-PCR technique was used for detection of PRRS virus and indirect ELISA technique was used for identification of the antigen - p125 of HC virus. Results of laboratory diagnosis showed that the PRRSV detected from pigs having clinical symptoms of PRRS were 84.03 percent. The PRRS virus was identified as North America type China strain. There were 6/119 samples simultaneously positive with both PRRSV and HC virus, accounting for 5.04 percent. The clinical signs of co-infected PRRS and HC were cyanosis in ears, hemorrhages in abdominal and inner thigh surfaces, convulsion, paralytic hindleg, severe hemorrhage in lungs, infarct spleen, petechiae kidney, hemorrhage in urinary bladder, mortality rate of co-infected PRRS and HC pigs was higher than that of pigs infected only with PRRS virus.