Mechanisms in which p-coumaric acid (CA) acts as an antioxidant are not well understood. This study investigated whether CA can act as a direct scavenger of reactive oxygen species (ROS) and whether it minimizes the oxidation of low-density lipoprotein (LDL). Rats were administered CA in drinking water at low or high doses for 10, 21, and 30 days (uptakes were 29 and 317 mg/day, respectively). Blood levels of 8-epiprostaglandin F₂ were monitored as a marker of LDL oxidation. Oral administration of CA (317 mg/day) for 30 days significantly inhibited LDL oxidation. CA also reduced LDL cholesterol levels in serum but had no effect on levels of high-density lipoprotein cholesterol. In vitro studies that used electron spin resonance in combination with spin trapping techniques were used to determine the ability of CA to scavenge ROS and alter LDL oxidation. CA effectively scavenged ·OH in a dose-dependent manner. IC₅₀ and maximum velocity for CA scavenging of ·OH were 4.72 µM and 1.2 µM/s, respectively, with a rate constant of 1.8 × 10¹¹ M¹ · s¹. Our studies suggest that the antioxidant properties of CA may involve the direct scavenging of ROS such as ·OH.