CD48 is a surface receptor (mCD48) expressed on most hematopoietic cells, as well as in a soluble form (sCD48). It seems to play a major role in asthma through the interactions of mast cells with eosinophils via its ligand CD244. Hence, this study was done to evaluate the role of CD48, in its membrane and soluble forms, as a novel biomarker in asthma with various degrees of severity. One hundred participants were enrolled in this study and divided into 4 equal groups matched in age and sex; mild asthma, moderate asthma, severe asthma and apparently healthy controls. All were investigated for blood leukocytes mCD48 expression using flow cytometry and sCD48 in serum using ELISA. Our results revealed that the sCD48 was significantly elevated in patients with mild asthma compared with the controls and the mild asthmatic groups (P<0.001). However, it was significantly decreased in severe asthma compared with moderate and mild asthma (P<0.001 and P=0.03, respectively). While it was significantly upregulated in severe asthmatic group compared to controls, patients with mild and moderate asthma on T-cell, B cells, Monocytes and NK cells (P<0.001 for all). In conclusion, CD48 may play a role in asthma and its level varies with severity of the disease being a useful marker in mild asthma.