Background: The thyroid gland and hormonal regulation are among the most important systems to be investigated in pre-term infants. This study sought to investigate thyroid hormone levels of healthy and unhealthy pre-term infants. Methods: The prospective study included 53 consecutive premature infants admitted to the neonatal intensive care unit within a duration of one year. Of these preterm babies, 20 were healthy, while 33 had problems such as asphyxia or RDS. Venous blood samples were collected at baseline 0-24 hours, 7 and 14 days and FT3, FT4, and TSH levels were determined. Other data recorded included demographic characteristics of the patients and clinical variables. Results: The most frequent health problems were RDS (87.9%), sepsis (30.3%), and retinopathy of prematurity (24.2%). The mean TSH levels showed a consistent decline at three consequent measurements in both groups, which were always significantly lower in unhealthy pre-terms. In both groups, TSH levels showed significant decreases on Day 7 and Day 14 compared to the baseline levels (p<005). The levels of FT3 and FT4 consistently showed significant correlations with gestational week and birth weight at each of the three measurements. Conclusion: Pre-term infants, especially those having problems, have significant hypothyroxinemia that may require thyroid hormone replacement therapy.