Porcine circovirus type 2 (PCV2) is the essential etiological agent of postweaning multisystemic wasting syndrome (PMWS), a worldwide distributed pig disease. The involvement of the immune system in the pathogenesis of PMWS is considered crucial. Previous studies have shown a cytokine profile suggesting T immunosuppression and indicating that interleukin 10 (IL-10) may play an important role during PCV2 infection. Nine 11- to 12-week-old conventional pigs were obtained from commercial farms located in North-Eastern Spain with historical records of PMWS. Spleen from four healthy and five PMWS-affected animals were collected at the necropsy. Viral load was determined in serum by means of standard PCR and real-time quantitative PCR. Phenotype and distribution of different immune cells involved in IL-10 secretion in the spleen of studied pigs were analysed using immunofluorescent assays. The CD163(+), CD4(+), and CD8(+) cell subpopulations produced IL-10 in the spleen and IL-10(+) cell numbers were higher in PMWS animals compared with their healthy counterparts. Furthermore, IL-10 producing cells were not infected by PCV2 and were mainly localized in the periarteriolar lymphoid sheaths. This is the first immunophenotyping study on IL-10 producing cells in cases of PMWS, further extending the studies on the role of IL-10 in disease pathogenesis.