Background: Thyroid hormones are very important through out neonatal period. Abnormal thyroid hormone levels have been reported in a variety of neonates with diseases other than thyroid gland pathology (Williams et al., 2004). The term ‘‘euthyroid sick syndrome’’ (ESS) or "nonthyroidal illness (NTI) syndrome" is used to describe a pattern of hormonal changes in the pituitary-thyroid axis in neonates without thyroid disease but with abnormal thyroid hormone levels. It has a variety of presentation. These changes could be an adaptive response to ‘stress’ which in turn may be beneficial to the sick patient (Economidou et al., 2011).The aim of this study was to evaluate the thyroid hormone profile and thyroid stimulating hormone in critically ill full-term neonates, investigate the possibility of using thyroid hormones profile in these patients as a prognostic marker of improvement or mortality, and to evaluate the thyroid profile of the survived patients to assess if these patients will need follow up and /or treatment.Material and Methods: Thyroid hormones and TSH were measured in the serum of neonates with critical illness at three samples (cases) and were compared with the level of thyroid hormones and TSH in healthy neonates (controls) and correlated to SNAP score.Results: Thyroid hormones levels were significantly lower in the cases than their levels in the controls, and continued to be lower till discharge or death in the cases compared to controls. Cases were then classified according to the level of thyroid hormones to two groups low TT3 alone and low both TT3 and TT4. This decrease in thyroid hormones correlates negatively with high SNAP score. The expired cases had worst thyroid hormonal profile from the disease beginning till death than the survived ones. The improved cases before discharge had a low level of free T4 comparing with that of controls. The TT3and TT4 level at the beginning of the disease can predict death in critically ill cases; so these observed thyroid hormones changes could be used as a prognostic marker of the fatal outcome of the patient.Conclusion: Thyroid hormones seem to be related to the severity of the disease and the unfavorable outcome in critically ill neonates. The TT3 and TT4 level were sensitive and specific parameters to predict death in critically ill cases. TT3 and TT4 level on admission could be added to SNAP score on admission to enforce its prognostic value in predicting outcome. This could help in using proper treatment from the start.