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Abstract Background: Postoperative cognitive dysfunction (POCD) is a frequent complication following brain tumor excision. Citicoline has neuroprotective properties, and selenium and zinc may enhance recovery after neurosurgical procedures. Objective: This research aimed to assess the impacts of selenium and citicoline versus zinc and citicoline versus citicoline alone on cognitive recovery in postoperative brain tumor excision patients in the ICU, and to compare the safety and adverse impacts of these supplementation strategies. Methods: This was a blind, prospective, randomized controlled study. Cases (n=144) undergoing brain tumor excision have been assigned to 1 of 3 groups: Selenium + Citicoline, Zinc + Citicoline, or Citicoline only. Cognitive function (MoCA scale), inflammatory markers (CRP, ESR), incidence of delirium, and ICU stay duration were assessed. Results: Selenium supplementation with citicoline led to the most favorable cognitive outcomes and greater reductions in inflammatory markers. The selenium group also had the lowest incidence of delirium and the shortest ICU stays. Conclusion: Selenium, followed by zinc, optimized postoperative cognitive recovery, reduced inflammation, and minimized delirium and ICU stay, suggesting that combining citicoline with antioxidants could enhance outcomes in patients undergoing brain tumor excision. Keywords: Postoperative cognitive dysfunction, Brain tumor excision, Citicoline, Selenium, Zinc, Neuroprotection, Inflammation.