Caffeic Acid Phenethyl Ester (CAPE) is a natural compound that has been found to exhibit anti‐proliferative, anti‐inflammative, and anti‐oxidant effects, although these effects have not been fully elucidated on cardiomyocytes. Oxidative stress in the heart contributes to the pathogenesis of various cardiovascular diseases, such as ischemia/reperfusion injury following a myocardial infarction. This study investigated the cardioprotective effects of CAPE against hydrogen peroxide (H2O2)‐induced oxidative injury in rat cardiomyocytes (H9c2) in pre‐treatment (24 hours before H2O2) and co‐treatment (with H2O2), and compared these activities to vitamin C, coenzyme Q10, and caffeic acid. Cell viability was evaluated after co‐treatment and pre‐treatment by a cell counting kit‐8 assay. H2O2 (300 μM to 500 μM) dose dependently decreased cell viability, and 500 μM H2O2‐treated cells (n=4) showed a significantly decreased cell viability of 16 ± 2% compared to control cells (p<0.05). By contrast, co‐treatment (n=5) and pretreatment (n=5) of cells with CAPE (5 to 40 μM) significantly reduced cell damage in a dose dependent manner by 24–29% ± 5–8% (p<0.05). However, co‐treatment and pre‐treatment of caffeic acid (1–40 μM. n=3), vitamin C (100–10,000 μM, n=4), and coenzyme Q10 (0.1–100 μM, n=3) did not show any significant protection on cardiomyocytes against H2O2. These preliminary results suggest CAPE can protect cardiomyocytes against oxidative stress induced by H2O2, which indicate CAPE as a potentially beneficial supplement to maintain cardiovascular health. We plan to investigate the mechanism of action of CAPE in future studies.Support or Funding InformationThis study was supported by the Center for Chronic Disorders of Aging, the Division of Research and the Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.