To investigate the effects of complex and prebiotic diets on nursery pigs inoculated for or vaccinated against porcine circovirus 2 (PCV2) on the intestinal health, 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 before arrival, while remaining pigs (PCV) were inoculated for PCV2 on d 0. Pigs were randomly assigned to 1 of 3 diets: complex (CO; lactose, spray-dried plasma, spray-dried whey), simple (SI; corn and SBM), or simple + 2.5% Grobiotic-S (GS). After 28 d of experiment, 1 pig per pen was euthanized by exposure to CO₂ for collection of samples. Two-cm segments of duodenum and ileum were collected for the determination of villous height (VH), villous area (VA), crypt depth (CD), and villous height:crypt depth (VH:CD) ratio. Images were recorded using an Olympus DP71camera (Olympus, Center Valley, PA). The VH, CD, VH:CD ratio, and VA were measured using Cell Sense standard software (Olympus, Center Valley, PA). For each intestinal sample, a minimum of 10 to 15 full villi and crypts were measured and averaged for statistical analysis. All data were analyzed as a completely randomized design using the MIXED procedure of SAS. Pen was considered the experimental unit and the model included treatment as a fixed effect. All measurements were performed without treatment awareness. No significant PCV-status effects were observed in the duodenum histological measurements; however, a significant diet × PCV-status interaction (P = 0.0251) on VH:CD in duodenal samples was observed. The highest VH:CD result observed was in pigs fed GS and inoculated with PCV. Diet had an effect (P = 0.0066) on duodenal CD, with deeper crypts being observed for GS pigs. With respect to VH and CD, a tendency for a diet × PCV-status interaction (P < 0.07) was observed whereby PCV inoculated pigs and fed simple or GS diets had greater CD and VH, respectively. No significant effects were observed for ileum histological measurements. Results indicate that diet complexity may affect duodenal health in pigs inoculated with PCV.