There is ongoing controversy as to whether hormonal changes of the euthyroid sick syndrome are predictors of poor outcome in sepsis and critical illness. In this prospective study, the prognostic accuracy of thyroid hormone levels in 103 critically ill adult patients on admission and during follow up in a medical intensive care unit (ICU) was assessed and was compared to clinical risk scores, namely, the acute physiology and chronic health evaluation and the simplified acute physiology score. Median T3 levels on admission to the ICU were lower in the 53 septic cases [0.9 nmol/l (IQR 0.6-1.1)] as compared with the 50 patients with a systemic inflammatory response syndrome [1.2 nmol/l (IQR 0.8-1.4), P < 0.001]. The lowest T3 levels were found in patients with severe sepsis [0.8 nmol/l (IQR 0.55-0.95)] and septic shock [0.8 nmol/l (IQR 0.6-1.0)]. There was no difference in T3 and free thyroxin (fT4) levels on admission in non-survivors compared with survivors overall and in subgroups of patients with SIRS and sepsis. During the follow up, fT4 levels decreased significantly in non-survivors, while they increased in survivors [fT4 difference -1.3 (IQR -2.5 to 0.2) vs. 0.8 (IQR -0.85 to 4.1), P = 0.003]. In addition, on the day of death, non-survivors had lower T3 and fT4 levels as compared with survivors (P = 0.04 and P = 0.02). T3 and fT4 levels on admission were not prognostic in this cohort of critically ill patients. A decrease in fT4 levels in the course of disease, however, may point to adverse outcome.