Interferon gamma (IFN-gamma) and nitric oxide (NO) are the major players of the host defense against Leishmania. In the present study circulating levels of IFN-gamma, NO, interleukin (IL)-6 and C-reactive protein (CRP) were compared in kala azar (KA), post-kala azar dermal leishmaniasis (PKDL) and healthy controls. A significantly elevated level of these parameters was evident in KA compared to PKDL or control. Further, significantly elevated levels of IFN-gamma, NO and CRP were observed in sodium antimony gluconate (SAG) unresponsive cases compared to responsive cases. In PKDL cases, NO was significantly elevated while other parameters were comparable to control. At post-treatment stage, KA patients showed a significant decrement in all the parameters, however, IL-6 and CRP remained above control level. Hence, data implies that the parasites survive in spite of the presence of effector molecules, and the excessive release of IFN-gamma and NO could be associated with the progression of the disease.