A 72-year-old female presented to the emergency room (ER) of Fatmawati Hospital with pneumonia and ketosis. After 12 h, her level of consciousness (LoC) decreased and she developed shortness of breath. In the ICU, antibiotics and supportive therapies were administered. After several hours, the need for vasopressors increased. Laboratory results showed severe lymphopenia, increased neutrophil to lymphocyte ratio (NLR) and D-Dimer levels. Septic shock and decreased LoC with severe immunoparalysis can be caused by intracranial process. A brain CT scan revealed massive ischemic stroke. Measures were taken to reduce intracranial pressure. Continuous Renal Replacement Therapy (CRRT) was performed for blood purification and immunomodulation. Vasopressor requirements decreased, her absolute lymphocyte increased and her NLR decreased. Diuresis and fluid balance were improved. She was subsequently discharged to the ICU. In this patient, massive ischemic stroke induced immunoparalysis, which manifested as lymphopenia and increased susceptibility to infection. Severe lymphopenia can be used as an early marker of ischemic stroke with signs of sepsis. © 2023 Faculty of Anaesthesia, Pain and Intensive Care, AFMS. All rights reserved.