Panulirus argus virus 1 (PaV1) is the only naturally occurring pathogenic virus in the Caribbean spiny lobster, Panulirus argus. The main targets of PaV1 are circulating hemocytes that serve as carriers for the systemic propagation of the virus . At the last stage of viral infection, PaV1 causes an important reduction in the total count of hemocytes, but the molecular alterations behind this process remain completely unexplored. In this study, we provide the first transcriptome-wide profile of changes occurring in hemocytes in P. argus at an advanced stage of PaV1 disease. By doing so, a total of 193 million high-quality reads were generated and assembled into 81,218 contigs. After statistical comparisons, 2733 transcripts were detected as differentially expressed, with 1284 down-regulated and 1449 up-regulated. Regarding the Biological Processes category of GO classification, down-regulated transcripts were enriched in GO terms involved in "immune response", "lipid metabolism", "cell adhesion", "protein repair", "catabolism", while up-regulated transcripts were associated with "protein phosphorylation", "ion transmembrane transport", "fucose metabolism", "carbohydrate metabolism", "G-protein coupled receptor signaling pathway", and "microtubule cytoskeleton organization". Transcripts involved in neuromodulation, lipid metabolism, and cell signaling were also affected in PaV1-infected hemocytes. This information provides a picture of the main molecular footprints altered by PaV1 in hemocytes during at a critical step of this disease, and represent a valuable genomic resource for this species.