The nursery pigs died successively after 10 days when they were transferred to fattening houses in a large-scale swine farm in Hunan Province. In order to confirm the epidemic and find out relevant pathogens，serum samples were collected from these pigs at different ages to detect antibodies against classical swine fever virus（CSFV），porcine reproductive and respiratory syndrome virus（PRRSV）and porcine circovirus virus 2（PCV2），meanwhile，four infected pigs were autopsied for observation，and pathological tissue samples were collected and pathogen detection of CSFV，PRRSV and PCV2，bacteria isolation and drug sensitivity analysis were carried out. The results showed that the level of antibodies against CSFV in pigs was not satisfying before and after the outbreak of the disease，which was lower in any individual pig，however，the pigs were detected to be CSFV-negative；generally，the maternal antibodies against PRRSV and PCV2 decreased and then increased when the epidemic took place，during which，positive samples of PRRSV and PCV2 were always detected out；meanwhile，Staphylococcus，Streptococcus and Haemophilus parasuis were isolated from the pathological tissues. It was concluded that the epidemic might be caused by mixed infection of PRRSV，PCV2 and other bacteria. Finally，the outbreak was effectively controlled by implementing prevention and control plans that were developped based on the above inference. In short，some references were provided for prevention and control of mixed infection with various pathogens in large-scale swine farms，and it was indicated that comprehensive prevention and control measures were required to be carried out in such large-scale farms.