Free Thyroxine as a Predictor of Mortality in Critically Ill Septic Patients—A Retrospective Study

<b>Background/Objectives:</b> Euthyroid sick syndrome (ESS), and particularly low T3, have been associated with increased mortality in septic patients, yet the prognostic value of free thyroxine (fT4) remains controversial. This study aims to evaluate the association between fT4 on ICU admission and mortality in septic patients. <b>Methods:</b> We conducted a single-center, retrospective observational study including 149 adult patients with sepsis or septic shock admitted to the Anesthesia and Intensive Care I Department of the Cluj County Emergency Hospital, Cluj-Napoca, Romania, between January 2019 and September 2025. Free T4 and thyroid-stimulating hormone (TSH) levels were measured within 24 h of ICU admission. The primary outcome was 28-day mortality, and the secondary outcome was in-hospital mortality. Demographic data, comorbidities, severity scores (SOFA, APACHE II), laboratory parameters, and outcomes were analyzed. Univariate and multivariate logistic regression analyses were performed, and predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). <b>Results:</b> A total of 149 patients were included. Twenty-eight-day mortality was 29.73%, and 53.57% in patients with sepsis and septic shock, respectively. Serum fT4 was significantly lower in non-survivors, for both primary and secondary outcome (<i>p</i> = 0.01 and <i>p</i> = 0.014, respectively), whereas TSH levels were similar between groups. In the univariate analysis, fT4 showed moderate predictive ability for mortality (AUROC 0.615 and 0.632). Multivariate models, including age, hemoglobin, SOFA score, and fT4, showed a greater discriminative performance (AUROC 0.805 and 0.799). <b>Conclusions:</b> Lower fT4 levels on ICU admission seem to be independently associated with increased mortality in septic patients. Incorporating fT4 into multiparametric prognostic models might improve early risk stratification in sepsis, particularly in settings where other thyroid parameters are not routinely available.