Serum Zinc and Selenium Are Independently Associated with Acute-Phase Inflammatory Markers in Critically Ill Patients: A Retrospective Observational Study

Background/Objectives: Zinc, selenium, copper, and manganese are essential cofactors for immune defense and redox homeostasis, yet their independent associations with routinely measured inflammatory markers in critically ill patients remain incompletely characterized. We aimed to examine these associations in intensive care unit (ICU) patients. Methods: This retrospective observational study enrolled 267 adult ICU patients at a single tertiary center. Serum trace element levels were measured at ICU admission and serially in a subset. Inflammatory markers—white blood cell count, neutrophil percentage, C-reactive protein (CRP), and procalcitonin—were measured concurrently. Hierarchical regression was performed at three adjustment levels, with Model 2 further adjusted for all remaining trace elements. A supplementary serial-level analysis used per-patient median concentrations. Results: In the fully adjusted model, zinc was independently and negatively associated with CRP (β = −0.68; 95% CI, −1.11 to −0.25; p = 0.002) and procalcitonin (exp[β] = 0.973; 95% CI, 0.961–0.986; p < 0.001), and selenium with CRP (β = −0.87; 95% CI, −1.48 to −0.25; p = 0.006). Copper showed a positive association with CRP exclusively in the fully adjusted model (β = 0.60; p = 0.006), consistent with ceruloplasmin’s role as a positive acute-phase reactant. Serial-level analyses corroborated these findings. No trace element was associated with neutrophil percentage. Conclusions: Lower serum zinc and selenium were independently associated with higher acute-phase inflammatory markers in critically ill ICU patients. These findings highlight the potential clinical relevance of trace element assessment in critically ill patients. Prospective studies are needed to determine whether targeted repletion can modify inflammation or improve clinical outcomes.