Low activity levels of the antioxidant enzyme, glutathione peroxidase (GPx), have been implicated in adverse clinical outcomes in coronary artery disease. A potential mechanistic link for this relationship is that low GPx activity predisposes patients to thrombotic complications due to impaired reactive oxygen species (ROS) metabolism. GPx potentially regulates the bioavailability of nitric oxide (NO) - a potent platelet inhibitor — therefore indirectly affecting platelet activation. This study examined the relationship between levels of GPx activity, ROS, and platelet activation in 51 acute coronary syndrome (ACS) patients. No relationship was observed between GPx activity and platelet reactivity nor between ROS levels and platelet reactivity. However patients with low GPx activity had significantly higher ROS levels (r2=0.1, p<0.05), suggesting a differential capacity to upregulate antioxidant defence in response to oxidative stress. Low levels of GPx activity may contribute to increased clinical risk by an inability to protect against oxidant-mediated damage.