The thrombus formation and oxidation of blood components caused by blood-contacting biomaterials were main reasons for poor hemocompatibility of biomaterials. To construct the anti-thrombotic and anti-oxidative surface, we electrospun styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS)/acylated Pluronic F127 (A-F127)/L-ascorbic acid (AA) microfibers based on the SEBS substrate in one step. Our strategy was based on that the phase-separation between SEBS and A-F127 during electrospinning resulted in hydrophilic surface of microfibers, the crosslinking of electrospun meshes rendered the surface stable, and the AA release from the microfibers interacted with blood cells actively to prevent blood cells from oxidative damage. We demonstrated that the self-assembly of SEBS/A-F127 blends resulted in the similar structure as core-shell microfibers with the A-F127 richness in the sheath; the presence of AF127 on the out layer made the microfibers hydrophilic and rendered the microfibers anti-thrombotic; the release of AA from the microfibers in the PBS solution was temperature-dependent; AA acted as the antioxidant to decrease the oxidative damage of blood cells after long-term contact between biomaterials and blood. Our work paves a new way to develop long-term hemocompatible biomaterials, which may be helpful to prevent blood cells from oxidative damage to maintain the normal function of blood cells in vivo. (C) 2018 Elsevier B.V. All rights reserved.