The present study was designed to assess the effect of orthognathic surgery on the immune system of patients suffering from dentofacial deformity. Osteoprotegrin (OPG) and transforming growth factor beta (TGF- ß) were utilized as calipers for assessment of the immunocompetence of patients following the surgical trauma of orthognathic surgery. Nine patients were selected from those attending the out-patient clinic of Oral and Maxillofacial Surgery Department, Faculty of Oral and Dental Medicine, Cairo University. Orthognathic surgery was performed to correct skeletal deformities, the surgical procedures Include: BSSO, Le fort 1 and genioplasty.Every patient went through different phases beginning by clinical diagnosis (history taking, clinical evaluation, photographs, radiographs), pre-operative orthodontic treatment, patient preparation (patients were psychologically prepared before surgery and subjected to pre-operative routine laboratory investigation before general anesthesia), model surgery, surgical procedure and follow up.The surgical procedure lasted from four to six hours and none of the patient experienced hemorrhage or needed blood transfusion and as regarding nerve injury or bad split it occurred once. All patients experienced periods of tolerable pain and oedema that decreased gradually after surgery and no incidence of wound infection or bone instability. OPG and TGF- ß levels were measured preoperatively; immediate post-operative, three days, one week, two weeks, four weeks and six weeks.The increasing in the levels of Osteoprotegrin (OPG) and Transforming growth factor beta (TGF- ß) was noticed throughout the post-operative periods and was significant compared to the pre-operative values. Regarding the obtained results the present study showed the immunosuppressive effect of orthognathic surgery.