The value of incorporating spray-dried plasma (SDP) into the diet of weanling pigs to improve feed intake and growth performance has been well documented. However, limited work has been done to confirm that the spray-drying process eliminates all viral contaminates including porcine circovirus type 2 (PCV2). To determine the effect of spray-drying on PCV2 infectivity, colostrum-fed, crossbred, specific-pathogen-free (SPF) pigs were inoculated with PCV2-contaminated SDP intraperitoneally (SDP-IP) or by oral gavage (SDP-OG), inoculated intraperitoneally with PCV2-positive plasma (POS), or left uninoculated (NEG). The plasma used for the experimentally produced SDP was collected from a SPF pig experimentally infected with a PCV2b isolate. Pigs in the NEG group remained seronegative, and PCV2 viremia was not detected. All pigs in the POS group became PCV2 viremic by 14 d postinoculation (DPI) and seroconverted by 28 DPI. In the SDP-IP group, all pigs became viremic by 35 DPI and seroconverted by 49 DPI. In the SDP-OG group, all animals became viremic by 35 DPI and 2/3 pigs seroconverted by 35 DPI. There were no significant (P > 0.05) differences between anti-PCV2-IgG antibody sample-to-positive ratios among pigs in the POS, SDP-OG, or SDP-IP groups. This work provides direct evidence that the experimental spray-drying process used in this study was not effective in inactivating PCV2b in the plasma of a PCV2-infected pig based on a swine bioassay using PCV2-naïve pigs. This work suggests that SDP sourced from pigs could represent a biosecurity risk for the industry.