The goal of this research project was to use Porcine Circovirus 2 (PCV2) challenge model as an approach to study the interaction of nutrition and disease (e.g., PRRS, mycoplasma pneumonia, salmonella, etc.). A total of 96 weaned barrows (age 27 to 40 d; BW 7.1 kg) were housed (4 pigs/pen) in an environmentally-controlled nursery with ad libitum access to feed and water over a 28-d study. Forty-eight pigs were vaccinated (VAC) for PCV2 prior to arrival, while the remaining 48 pigs (PCV) were inoculated with PCV2 on d 0. Pigs were randomly assigned to 1 of 3 dietary treatments: 1) complex diet (CO; lactose, spray-dried plasma, spray-dried whey); 2) simple diet (SI; corn and SBM); or 3) prebiotic diet (GS; SI + 2.5% Grobiotic-S). From the data obtained in this experiment, the main conclusions are as follows: 1) As evidenced by reduced BW, ADFI, and ADG in PCV2-inoculated pigs compared to PCV2-vaccinated pigs, the PCV2-challenge model that was implemented was efficacious with respect to the utility of this model for future efforts in exploring nutrition × health interactions; 2) As expected, changes in immune biomarkers were consistent with PCV2 disease progression; and 3) The observation that there are transient and conflicting effects of time, diet, and PCV-status on feed efficiency indicates that digestibility may be reduced in PCV-challenged pigs and that this model may be used in the future to manipulate the diet to help facilitate greater assimilation of nutrients in pigs faced with a disease challenge