To perform global transcriptome profiling using RNA-seq in the peripheral blood of intracerebral hemorrhage (ICH) patients. In 11 patients with ICH, peripheral blood was collected within 24 h of symptom onset or last known well, and a second blood draw occurred 72 h (±6) after the first. RNA-seq identified differentially expressed genes (DEGs) between the first and second samples. Biological pathway enrichment analysis was performed with Ingenuity^® Pathway Analysis (IPA). A total of 16,640 genes were identified and 218 were significant DEGs after ICH (false discovery rate <0.1). IPA identified 97 disease and functional categories that were significantly upregulated (z-score >2) post-ICH; 46 categories were specifically related to immune cell activation, 22 to general cellular activation processes, and 4 to other inflammation-related responses. In the canonical pathway and network analysis, inflammatory mediators of particular importance included interleukin-8, NF-κB, ERK1/2, and members of the integrin class. ICH induced peripheral blood gene expression at 72 to 96 h compared with 0 to 24 h from symptom onset. DEGs that were highly expressed included those related to inflammation and activation of the immune response. Further research is needed to determine whether these changes affect outcomes and may represent new therapeutic targets.