Rheumatic fever is a chronic inflammatory multifactorial disease which may lead to rheumatic carditis and permanent valve damage. Our study included 50 patients with acute rheumatic fever and 50 patients with rheumatic heart disease ; they were 58 females and 42 males ranging in age from 5 to 18 years. 50 age matched healthy children were included as controls. Using ELISA technique, we studied the changes in the serum level of collagen I, collagen III, laminin and hyaluronic acid as new rheumatic fever markers more prominent and relevant for early detection and diagnosis. The results were analyzed statistically and revealed that there is a highly significant increase in the serum level of collagen I, collagen III, laminin and hyaluronic acid in patients with acute rheumatic fever and rheumatic heart disease. Moreover, we found a highly significant statistical correlation between these biochemical markers and the clinical severity of the disease.