Clinicians have used additional tools to aid clinical assessment and to enhance their ability to identify the “vulnerable” patient at risk for cardiovascular diseases. Circulating biomarkers are one such tool used for identifying better high-risk individuals and to prognosticate effectively and treat patients with disease. A persistent immune activation is a main feature of atherosclerosis. The inflammatory activity is not only detectable in the vascular wall, but also in peripheral blood. Patients with coronary artery disease show increased numbers of neutrophils and T cells as well as elevated levels of several inflammatory mediators. On the other hand, several cardiovascular disease states show a daily cycle of activity, i.e. a peak incidence of cerebrovascular and cardiovascular events has been documented in the early morning hours. Several studies have shown diurnal variations in inflammatory systemic markers in patients with acute coronary syndrome. Diurnal variations can alter the analysis of blood-derived samples. Prior to the analysis of a blood sample, multiple steps are necessary to generate the desired specimen. The knowledge of diurnal variations is a prerequisite to understand and control their impact. This brief review comments the effect of the diurnal variation on the most important inflammatory systemic biomarkers in the setting acute coronary syndrome: interleukin-6, neopterin, matrix metalloproteinases, vascular cell adhesion molecule-1, intercellular adhesión molecule-1, soluble CD40 ligand, and C-reactive protein.