Central hypothyroidism is a thyroid hormone deficiency due to a disorder of the pituitary, hypothalamus or hypothalamic -pituitary portal system, leading to diminished thyroid –stimulating hormone (TSH), thyrotropin–releasing hormone (TRH) or both. It has an estimated prevalence of approximately 1 in 100.000. It is rarely isolated and occurs more commonly in conjunction with other pituitary hormones deficiency as well as neurological signs. The clinical manifestations of isolated central hypothyroidism are usually non -specific and are often delayed or miss diagnosised. The diagnosis can be difficult and usually based on low level of free hormone (FT4) and low to normal level of thyroid –stimulating hormone (TSH). The diagnostic value of Thyrotropin –releasing hormone (TRH) test has been evaluated in such situation. The screening, in the majority relay on TSH measurement. In this article we describe three infants who were diagnosed with congenital isolated central hypothyroidism at the KKUH, Riyadh, Saudi Arabia during the period from January 2016 to April 2019, as pediatricans need to be aware of this rare condition to avoid diagnostic delay and to start the appropriate replacement therapy