Movement of beef calves from a pasture to a housing environment induces a stress response including changes in leukocyte physiology. Understanding the molecular profiles underlying these changes can help to develop better management practices and treatments to minimize the deleterious effects of stress. The objective of this study is to characterize the leukocytes transcriptome changes during housing stress after moving claves from outdoor to indoor environments. Transcriptome of blood leukocytes from 6 beef calves in outdoor pasture (d 0) was compared with that of d 1, 2 and 7 after being moved indoors. Individual calf RNA-seq libraries were sequenced using Illumina HiSeq analyzer platform. Single-end reads were mapped to the Bos taurus reference genome (UCSC_bosTau7) using Tophat v2.0.12. In total, 26,163 isoform transcripts pertaining to 8,606 genes were identified and 1,636 isoform transcripts pertaining to 1,320 genes were differentially expressed at d 1, d 2 and d 7 relative to d 0 (False Discovery Rate-adjusted P-value <0.05) using Cufflinks v2.2.1. The number of differentially expressed genes increased with time indoors: d 0 vs d 1 (32 genes), d 0 vs d 2 (434 genes), and d 0 vs d 7 (1170 genes). Among the top 50 differentially abundant transcripts CCAAT/enhancer binding protein C/EBP epsilon (CEBPE) and Dual Specificity Phosphatase 1 (DUSP1) were overexpressed in leukocytes collected on d 1, d 2, and d 7, relative to d 0. DUSP1 plays a role in the cellular response to environmental stress, and CEBPE is essential for terminal differentiation and functional maturation of leukocyte cells. Functional analysis of the differentially expressed genes using DAVID identified 8 enriched functional category clusters pertaining to Biological Processes, Molecular functions and KEGG Pathways (Enrichment score >2): protein synthesis and transport, cell regulation and reorganization, RNA transport, leukocyte activation, proliferation and differentiation. These categories confirm that housing stress elicits changes in the leukocyte transcriptome associated with inflammatory response. The permanency of these changes and the impact on inflammatory response to other stress sources including infection and management requires further evaluation.