Sick premature infants may display transient hypothyroxinemia secondary to immaturity of the hypothalamic-pituitary axis. Therefore, early screening programs of such infants may be misleading. We present such a case report, with review of the literature and the following suggested recommendations. (1) Screening programs should report thyroid-stimulating hormone (TSH) as well as thyroxine (T(4)) levels in premature infants, which will allow the treating physicians to be aware of possible abnormality that needs to be followed. (2) Sick premature infants and other populations at risk should undergo a full serum thyroid function evaluation including free T(4) and TSH beyond the screening program at discharge or at 30 days of age, whichever comes first. (3) Physicians should use their clinical judgment and experience even in the face of normal newborn thyroid screening test and reevaluate for hypothyroidism when there is a clinical suspicion. Our case report is a reminder of the American Academy of Pediatrics guidelines with practical suggestions for extra caution to avoid missing primary hypothyroidism in sick premature infants.