Measles virus continues to cause morbidity and mortality despite the existence of a safe and efficacious vaccine. Measles is associated with induction of both a long-lived protective immune response and immunosuppression. To gain insight into immunological changes during measles virus infection, we examined gene expression in blood mononuclear cells from children with acute measles and children in the convalescent phase compared to uninfected control children. There were 13 significantly upregulated and 206 downregulated genes. Upregulated genes included the immune regulatory molecules interleukin 1beta (IL-1beta), CIAS-1, tumor necrosis factor alpha, PDE4B, PTGS2, IL-8, CXCL2, CCL4, ICAM-1, CD83, GOS-2, IER3 (IEX-1), and TNFAIP3 (A20). Plasma levels of IL-1beta and IL-8 were elevated during measles virus infection. Downregulated genes mainly involved three gene ontology biological processes, transcription, signal transduction, and the immune response, and included IL-16 and cell surface receptors IL-4R, IL-6R, IL-7R, IL-27RA, CCR2, and CCR7. Most mRNAs had not returned to control values 1 month after discharge, consistent with prolonged immune response abnormalities during measles virus infection.