Objectives: To clarify the possible of Injectable calcium phosphate cement bone substitute on salivary immunoglobulin A and interleukin-6 in minor oral surgery.Study design: Twenty patients suffering from impacted mandibular third molar. They were selected from those attending the out patient clinic, Department of Oral and Maxillofacial Surgery, Faculty of Oral and Dental Medicine, Cairo University. Have moderately difficult impacted lower third molar according to modified difficulty index of Pederson, medically free from any systemic disease and with age range from 20-35 years. Divided into two equal groups, group I was surgically operated and the socket of the impacted tooth was closed without insertion of bone substitute, group II was surgically operated and the socket of impacted mandibular third molar was packed with injectable calcium phosphate cement bone substitute. The effect of the injectable calcium phosphate bone substitute on the oral and serum immunocompetance was assessed by sample collected from the serum and mixed non-stimulated whole saliva at the following intervals; Preoperative, two hours postoperative, one week and two weeks postoperative. The collected data of serum Interleukin-6 (IL-6) and salivary Immunoglobulin-A (sIgA) were tabulated and statistically analyzed.Results: On comparison of preoperative mean value of IL-6 and sIgA between group I and group II it was detected that, there is no significant difference between them. On comparison the mean value of IL-6 and sIgA at different time interval between the two groups, it was detected that, there is no significant difference between them.Conclusion: The present study revealed that injectable calcium phosphate cement utilized a model of minor oral surgery represented by surgical removal of impacted mandibular third molar has no significant immunological effect.