Rationale: Rhodococcus equi is an intracellular bacterium that causes pneumonia in young foals. Current research on understanding the host response has been limited to the evaluation of few cytokines, selected candidate genes and certain cell types like neutrophils and macrophages. Hence, a high throughput tool like the expression microarray may yield gene signatures and identify molecular pathways that may potentially contribute to disease susceptibility. Objective: The purpose of this study was to determine the expression profile associated with blood leukocytes and nasal epithelial cells in affected and healthy foals in order to obtain discriminating molecular biomarkers for disease onset. Methods: Peripheral blood leukocytes and nasal epithelial cells from six affected and six unaffected foals were obtained at birth, two and four weeks time points. RNA was extracted and the generated cDNA was labeled with fluorescent dyes and hybridized to the equine whole genome microarray. Results: Results obtained from blood leukocytes suggests that at birth biological processes associated with differentially expressed genes highlight immunity towards T-helper 2 response, reduced T-cell proliferation and IFN-γ production that may lead to increased disease susceptibility. At week-2, antibacterial inflammatory markers become evident while at week-4 genes involved in lymphocyte development, defense and iron ion homeostasis were observed. For all three time points in nasal epithelial cells, the biological processes point towards a reduced T-cell proliferation and inflammatory response. Conclusions: Findings led to the identification of genes and processes that may contribute to foal susceptibity and provided molecular biomarkers that differentiate susceptible foals early in life.