Bacterial and/or viral co-infections are very common in swine production and cause severe economic losses. , and are pathogenic bacteria that may be found simultaneously in the respiratory tracts of pigs. In the present study, the interactions of with epithelial and phagocytic cells in the presence or absence of a pre-infection with and/or were studied. Results showed relatively limited interactions between these pathogens. A previous infection with one or both mycoplasmas did not influence the adhesion or invasion properties of in epithelial cells or its resistance to phagocytosis (including intracellular survival) by macrophages and dendritic cells. The most important effect observed during the co-infection was a clear increment in toxicity for the cells. An increase in the relative expression of the pro-inflammatory cytokines IL-6 and CXCL8 was also observed; however, this was the consequence of an additive effect due to the presence of different pathogens rather than a synergic effect. It may be hypothesized that if one or both mycoplasmas are present along with in the lower respiratory tract at the same time, then increased damage to epithelial cells and phagocytes, as well as an increased release of pro-inflammatory cytokines, may eventually enhance the invasive properties of . However, more studies should be carried out to confirm this hypothesis.