Piscirickettsiosis is the main bacterial disease affecting the Chilean salmon farming industry and is responsible for high economic losses. The aim of this study was to describe and comparatively quantify the immune response of post-smolt Atlantic salmon infected by cohabitation with fish bearing LF-89-like and EM-90-like Piscirickettsia salmonis. The expression of 17 genes related to the immune response was studied in head kidney from cohabitant fish by RT-qPCR. Our results at the transcriptomic level suggest that P. salmonis is able to manipulate the kinetics of cytokine production in a way that might constitute a virulence mechanism that promotes intracellular bacterial replication in cells of Atlantic salmon. This strategy involves the creation of an ideal environment for the microorganism based on induction of the inflammatory and IFN-mediated response, modulation of Th1 polarization, reduced antigen processing and presentation, modulation of the evasion of the immune response mediated by CD8+ T cells and promotion of the CD4+ T-cell response during the late stage of infection as a mechanism to escape host defences. This response was significantly exacerbated in fish infected by PS-EM-90 compared with fish infected by PS-LF-89, a finding that is probably associated with the higher pathogenicity of PS-EM-90.