<p>Selenium is an essential trace element involved in antioxidant defense and immune regulation, yet its clinical role in critically ill patients remains uncertain. In this prospective single-center observational study, we evaluated 144 ICU patients between March 2022 and October 2023. Serum selenium levels were measured, and eligible patients received intravenous selenium supplementation (1000&#xa0;µg/day for 5 days). Clinical outcomes, including ICU mortality, were analyzed in relation to selenium status and response. Selenium levels &lt; 70&#xa0;µg/L were observed in 27.8% of patients and were associated with higher severity scores, inflammatory markers, and longer hospital stay. Among 67 patients receiving supplementation, those with a post-treatment selenium increase &gt; 50&#xa0;µg/L had significantly lower ICU mortality. Multivariate analysis identified SOFA score, FiO₂, and selenium increase as independent predictors of ICU mortality. Lower selenium levels were associated with greater illness severity, and adequate selenium repletion may be linked to improved outcomes. However, the study is limited by its non-randomized, single-center design and relatively small sample size.</p>