Mycobacterium tuberculosis can cause life-threatening complications in which the immune response plays an important role. This study was designed to evaluate the serum levels of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and soluble Fas (sFas) in cases with pulmonary tuberculosis due to confirmed M. tuberculosis infection. The study comprised 50 patients with M. tuberculosis classified to 13 complicated cases and 37 uncomplicated patients. A significant (P<0.05) increase was found in the serum levels of IL-18, IFN-gamma and sFas in patients compared to controls and also in complicated cases compared to uncomplicated ones. Moreover, a positive significant correlation was found between serum levels of sFas with IL-18 (r=0.532, P<0.001), and with IFN-gamma (r=0.37, P=0.008) and lastly between serum levels of IL-18 with IFN-gamma (r=-0.612, P<0.001). It is concluded from these results with the recent observations that IFN-gamma levels are elevated after successful MTB treatment, suggest the possibility of enhanced Fas expression and then stimulating the infected macrophages to show an increased FasL-induced apoptosis. Modulation of FasL system by M. tuberculosis might represent an escape mechanism to evade the effect of apoptosis. Moreover, the elevated serum levels of IL-18, IFN-gamma and sFas can be considered as pathognomonic markers suggesting pulmonary tuberculosis especially in complicated cases.