A bstract Introduction The aim of this study was to determine the prognostic value of admission immunosuppressive acidic protein (IAP), interleukin-6 (IL-6), total oxidant status (TOS), and total antioxidant status (TAS) in 161 critically ill patients. Materials and methods This prospective observational study was carried out in the Emergency Department ICU for 6 months. Critically ill patients were included in the study consecutively. The main outcomes were the need for early mechanical ventilation (MV) and in-hospital mortality. Results The mean age of 161 patients was 66.5 ± 17.1 years. The median IL-6 levels of patients who required early MV were significantly higher than of the patients who required no MV ( p < 0.001), and the median IL-6 levels in the nonsurvivors were significantly higher than in the survivors ( p < 0.001). The median IAP levels were not significantly different between the groups ( p = 0.464 for early MV and p = 0.340 for the in-hospital mortality group). The AUCs of IL-6 and TOS for predicting in-hospital mortality were 0.819 and 0.608, respectively. Conclusion The IAP level on admission to ICU is ineffective in predicting the need for early MV and in-hospital mortality; however, IL-6 level on admission is a strong prognostic predictor in critically ill patients. Our findings showed that the burden of oxidative stress was high in general ICU patients. Clinical significance Our study showed that increased oxidative stress is an important problem in critically ill patients. If measures are taken to reduce oxidative stress by physicians, the prognosis of critically ill patients will be better. How to cite this article Tutuncu EO, Dundar ZD, Kilinc I, Tutuncu A, Kocak S, Girisgin AS. Prognostic Value of Immunosuppressive Acidic Protein and Oxidative Stress Status in Critically Ill Patients. Indian J Crit Care Med 2021;25(4):405–410.