Background: Septic shock is a recognized cause of global mortality in intensive care units. Sedation and analgesia management are essential for patients with sepsis or hemodynamic instability. Although considered safe concerning hemodynamic changes, ketamine use might cause a substantial rise in intracranial pressure (ICP). Methods: An interventional study was conducted at the intensive care unit of Zagazig University Hospitals from December 2021 to March 2023 and covered 100 adult patients with septic shock requiring mechanical ventilation, sedation, and vasopressors. Patients with acute brain injury were excluded. Noninvasive ICP including ICP derived from pulsatility index, ICP derived from diastolic flow velocity (ICPFVd), and ICP derived from optic nerve sheath diameter, and hemodynamic monitoring were measured before adjunct low-dosage (0.3 mg/kg/hr) continuous ketamine infusion (T0), after 12 h (T1), and after 24 h of infusion (T2). Results: Baseline ICP derived from optic nerve sheath diameter, ICP derived from pulsatility index, and ICPFVd medians were 14.5 (interquartile range [IQR] 7), 16.8 (IQR 0.91), and 13.8 (IQR 9.38) mm Hg, respectively. Only ICPFVd showed a significant slight increase from 13.75 (IQR 8.5) at T1 to 13.90 (IQR 8.5) at T2 (P value=0.042). The baseline median noninvasive cerebral perfusion pressure was 74.56 (IQR 12.39) mm Hg without significant change at T1 or T2 (P value=0.09). The respiratory rate, heart rate, and mean arterial blood pressure showed no significant changes across timepoints (P values=0.95, 0.86, and 0.14, respectively). The median doses of midazolam, fentanyl, and norepinephrine significantly decreased across the study timepoints, especially at the first 12 h (P value<0.001 for each). Conclusions: The present pilot study showed promising results of low-dose continuous ketamine infusion adjunctly on ICP and hemodynamics with a substantial reduction of sedatives and vasopressor dose. Further studies with large sample sizes and longer duration of administration and follow-up are needed to expand the current findings