Porcine circovirus 2 (PCV-2) is a primary agent of post-weaning multi-systemic wasting syndrome (PMWS), ubiquitous in pig herds. The course of viraemia and seroconversion in naturally infected pigs were investigated in piglets from the 2nd week of their life. Piglets were divided into seropositive (Ab+) and seronegative (Ab−) groups. Subsequently, after vaccination against PCV-2 (Ingelvac® CIRCOFLEX™, Böehringer Ingelheim), they were further divided into non-vaccinated seronegative (NVAC/Ab−) and seropositive (NVAC/Ab+), and vaccinated seronegative (VAC/Ab−) and seropositive (VAC/Ab+). PCV-2 colostral antibodies failed to prevent development of natural PCV-2 infection in conventional piglets; however, this occurred at a higher age in comparison with seronegative pigs. Neither colostral nor post-infection antibodies prevented development of viraemia, which persisted up to the end of the study (the 19th week), but without clinical signs of PMWS. Vaccination failed to prevent development of natural PCV-2 infection, but viraemia was limited to between the 8th and 10th week. The presence of colostral anti-PCV-2 antibodies did not show any untoward effect to vaccination; on the contrary, VAC/Ab+ animals showed the lowest titre of viraemia.