Two prospective longitudinal studies in 13 postweaning multisystemic wasting syndrome (PMWS)-affected farms from Spain (n= 3) and Denmark (n= 10) were performed. Blood samples from pigs were longitudinally collected from 1st week until the occurrence of the PMWS outbreak. Wasted and healthy age-matched pigs were euthanized, necropsied and histopathologically characterised. PMWS diagnosis was confirmed by means of lymphoid lesions and detection of porcine circovirus type 2 (PCV2) in these tissues by in situ hybridization or immunohistochemistry. Serological analyses were performed in longitudinally collected serum samples to detect antibodies against, PCV2, porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), swine influenza virus (SIV) and Lawsonia intracellularis (law), Mycoplasma hyopneumoniae, Aujeszky's disease virus (ADV) and Salmonella spp. A Cox proportional hazards model was used to investigate the simultaneous effects of seroconversion and maternal immunity against the studied pathogens. Results showed that high levels of maternal immunity against PCV2 had a protecting effect in farms from both countries. Moreover, for the Danish dataset, seroconversion against law had an overall protecting effect, but for animals with very low levels of maternal antibody levels against this pathogen, the effect appeared neutral or aggravating. Otherwise, for the Spanish dataset, maternal immunity against PPV and PRRSV gave protective and aggravating effects, respectively. In conclusion, the present study reflects the complex interaction among different pathogens and their effects in order to trigger PMWS in PCV2 infected pigs.