Background: Coronary Artery Disease results from accumulation of atheroma that reduces blood flow leading to ischemia and later infarction. Cardiac enzymes like cardiac troponin I and creatinine kinase MB are measured to further establish the diagnosis but not its prognosis. IL-6 increases at an early stage of atherosclerosis and peaks during myocardial infarction. Alkaline phosphatase is responsible for dephosphorylation of pyrophosphate, a calcification inhibitor which leads to calcification of blood vessels. Aim: This study is to investigate serum levels of IL-6 and ALP and their connection to the severity of CAD and also to determine if IL-6 and ALP are correlated or independent predictors of the severity of CAD. Methods: Fasted blood samples were collected to test for IL-6 and Alkaline Phosphatase from August 2016 to February 2017 in 80 patients with positive results of coronary angiographies at Qilu Hospital of Shandong University and divided into four groups; control (20), stable angina (20), unstable angina (20) and acute myocardial infarction (20). Results: IL-6 and CAD showed a significant relationship with a p value of 0.018 (P value < 0.05). Additionally, ALP and CAD showed a very significant relationship (P < 0.001). However, IL-6 and ALP yielded a negative correlation coefficient value (r= -0.032) and p value was 0.779 (P > 0.05). Conclusion: Results from our study showed that there is a significant correlation between both IL-6 and ALP to the severity of CAD. However, there is no relationship between IL-6 and ALP as their role in CAD progression is independent of each other.