Sixty-seven pigs were randomly assigned to four groups. Group 1 served as negative control pigs, group 2 pigs were inoculated with Mycoplasma hyopneumoniae (M. hyopneumoniae), group 3 pigs were dually-inoculated with M. hyopneumoniae and porcine circovirus type 2 (PCV2) and group 4 pigs were inoculated with PCV2. Dual-infected pigs had moderate dyspnea, lethargy, and reduced weight gain. The overall severity of PCV2- associated microscopic lesions in lung and lymphoid tissues were significantly (p<0.05) higher in the dualinfected pigs compared to all other pigs. Four of 17 dual infected pigs had lesions consistent with postweaning multisystemic wasting syndrome (PMWS) whereas none of the singular PCV2-infected pigs developed PMWS. This study indicates that M. hyopneumoniae potentiates the severity of PCV2-associated lesions and increases the incidence of PMWS. This co-infection model closely mimics the field situation were co-infections with PCV2 are commonly observed. In the future this model will be very useful for testing intervention strategies for the control of PCV2-associated disease in growing pigs.