CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of different immune cells. They are known to play crucial roles in antibody class switching in B cells, neutrophil recruitment and activation of macrophages and CD8+ cytotoxic T cells. The activation and functional status of CD4+ T cells is important for adequate responses to pathogen infections but has also been associated with auto-immune disorders and survival in several cancers. In the current study, we carried out proteomic profiling of resting and activated primary human CD4+ T cells from healthy donors. In addition to identifying known markers of CD4+ T cell activation, we also identified protein kinases, protein phosphatases, and cytokines to be differentially expressed.