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Abstract: Background: A determination of serum Transthyretin (TTR, Prealbumin) level is an objective method of assessing protein catabolic loss of severely ill patients and numerous studies have shown that TTR levels correlate with patient outcomes of non-critically ill patients. We evaluated whether TTR level correlates with the prevalence of PEM in the ICU and evaluated serum TTR level as an indicator of the effectiveness of nutrition support and the prognosis in critically ill patients. Methods: We studied PEM prevalence in 118 patients admitted to a community hospital''s medical intensive care unit and the association between TTR, low albumin (ALB) concentration and high-risk disease (HRD), i.e., sepsis, inability to take in oral nutrients, etc. Serum TTR was measured on the day of admission, day 3 and day 7 of their ICU stay. APACHE II and SOFA score was assessed on the day of admission and the nutritional status and nutritional requirement was assessed for their entire ICU stay. Patients were divided into three groups based on initial TTR level and the outcome analysis was performed for APACHE II score, SOFA score, ICU length of stay, hospital length of stay, and mortality. Results: TTR showed excellent concordance with patients classified with PEM or at high malnutrition risk, and followed for 7 days, it is a measure of the metabolic burden. TTR levels decline from day 1 to day 7 in spite of providing nutritional support. Patients were classified in 3 categories with respect to the level of TTR: more than 170 mg/L, twenty-five patients (group 3); 100–170 mg/L, forty-eight patients (group 2); less than 100 mg/L, forty-five patients (group 1). TTR level correlated with ICU length of stay, hospital length of stay, and APACHE II score, and predicts mortality. Conclusions: TTR identified patients at highest risk for metabolic losses associated with stress hypermetabolism as serum TTR levels did not respond early to nutrition support because of the delayed return to anabolic status. It is particularly helpful in removing interpretation bias, and it is an excellent measure of the systemic inflammatory response concurrent with a preexisting state of chronic inanition. [Copyright &y& Elsevier]