The generation of autoantibodies against chromatin is a hallmark of the multifactorial autoimmune disease systemic lupus erythematosous (SLE). Impaired clearance of apoptotic cells together with the release of nuclear autoantigens are supposed to contribute to the loss of self-tolerance in SLE. Phospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) are exposed on the surfaces of apoptotic cells and on apoptotic blebs. Also histones/nucleosomes can be detected on apoptotic cells; however, their binding motifs are still unknown. Therefore, we investigated the interaction of PS, PE, phosphatidylcholine (PC), and cardiolipin (CL) with histones H1, H2A, H2B, H3, and H4 by surface plasmon resonance (SPR). Strong binding to phospholipids was found for all histones, with H2A displaying the highest binding affinity to all phospholipids investigated. Hence, phospholipids including PS and PE may contribute to the binding of histones to surfaces and blebs of apoptotic cells. Moreover, histones/nucleosomes complexed to uningested apoptotic membrane structures may foster autoimmunity towards nuclear compounds.