Objective: The aim of this study was to compare highsensitivity C-reactive protein (hsCRP) and Lipoprotein(a) levels [Lp(a)] levels between diabetic and non-diabetic patients with coronary artery disease (CAD). Study Design: Cross sectional Study. Place and Duration of study: This study was conducted in the department of Physiology of College of Medicine & King Khalid University Hospital, King Saud University, Riyadh between August 2006 and December 2007. Methods: One hundred and three individuals with CAD and 30 healthy individuals matched for age and BMI were studied. CAD patients were divided into two groups based on presence (n=62) and absence (n=41) of type 2 diabetes mellitus. Overnight fasting blood samples were collected, and analyzed for total cholesterol (TC), Triglycerides (TG), Low density Lipoprotein (LDL) and High density lipoprotein (HDL), Lp(a) and hsCRP. Data about CAD severity was obtained from medical records. Results: Both groups of CAD without and with DM had significantly higher levels of Lp(a) [mg/dl] (25.58 ± 25.99, 25.90 ± 24.67 respectively) and hsCRP [mg/dl] (0.52 ± 0.71, 0.82 ± 0.78 respectively) when compared with healthy control subjects (Lp(a) =16.93 ± 15.34 & hsCRP=0.27 ± 0.21) [p<0.05]. Lp(a) levels between the two CAD groups were non significant. While, hsCRP levels were significantly high in CAD with DM compared to those without DM [p<0.05]. Gensini Score of CAD severity was also higher in CAD with DM [67.60 ± 45.94] than those without DM [52.05 ± 42.27, p<0.05]. Conclusion: Elevated Lp(a) and hsCRP levels are associated specifically with angiographically defined CAD. However, hsCRP elevation but not Lp(a) is also associated with CAD in type 2 diabetes mellitus. Measurement of hsCRP and Lp(a) may be considered optional markers for better prediction of cardiovascular risk.