Lipids are key regulators of immune responses. In this study we investigated the direct impact of oxidized phospholipids (ox‐PL) on T cell activation and function. We could demonstrate that ox‐PL strongly inhibit proliferation of purified human T cells induced with anti‐CD3/CD28 or anti‐CD3/CD63 mAb, whereas proliferation of naive T cells from human cord blood was not affected by ox‐PL. Unoxidized phospholipids showed no such effect. Inhibition of T cell proliferation by ox‐PL was not due to cell death. Moreover, T cell proliferation triggered by PMA/ionomycin activation was not diminished by ox‐PL. T cells activated in the presence of ox‐PL produced and released low amounts of IFN‐γ and IL‐2, whereas IL‐4 was only slightly diminished. Ox‐PL prevented the expression of de novo synthesized activation markers (CD25, MHC class II) but not expression of CD63 or CD69. We further observed that T cells stimulated in the presence of ox‐PL are poorly cytotoxic T cells. Most importantly, T cells activated in the presence of ox‐PL failed to proliferate in response to restimulation. This hypo‐proliferative state was accompanied with an up‐regulation of early growth response gene 3 and Casitas B‐lineage lymphoma protein B. Taken together, our results demonstrate that ox‐PL are potent and specific regulators of T cell activation and function.