Aphanomyces invadans, the causative agent of epizootic ulcerative syndrome, is one of the most destructive pathogens of freshwater fishes. To date, the disease has been reported from over 160 fish species in 20 countries and notably, this is the first non-salmonid disease that has resulted in major impacts globally. In particular, Indian major carps (IMCs) are highly susceptible to this disease. To increase our knowledge particularly with regards to host immune response against A. invadans infection in a susceptible host, the gene expression profile in head kidney of A. invadans-infected and control rohu, Labeo rohita was investigated using RNA sequencing. Time course analysis of RNA-Seq data revealed 5608 differentially expressed genes, involved among others in Antigen processing and presentation, Leukocyte transendothelial migration, IL-17 signaling, Chemokine signaling, C-type lectin receptor signaling and Toll-like receptor signaling pathways. In the affected pathways, a number of immune genes were found to be downregulated, suggesting an immune evasion strategy of A. invadans in establishing the infection. The information generated in this study offers first systematic mechanistic understanding of the host–pathogen interaction that might underpin the development of new management strategies for this economically devastating fish-pathogenic oomycete A. invadans.