Formerly termed euthyroid sick syndrome, non-thyroidal sickness syndrome (NTIS) is a disorder that frequently occurs in acute or chronic illnesses that alter the levels of thyroid hormone and patterns, even in the absence of hypothalamic-pituitary-thyroid axis problems or diseases. The primary findings on the thyroid hormone panel in NTIS are elevated reverse T3 (rT3) and decreased triiodothyronine (T3) levels, which may be followed by other thyroid hormone abnormalities, such as thyroid-stimulating hormone (TSH) and thyroxine (T4). The incidence of NTIS increases among hospitalized patients with critical illness, and there is an associated increase in mortality. NTIS is also associated with worsening outcomes during and after treatment in patients hospitalized with infectious or non-infectious diseases, such as cardiovascular, kidney, lung, diabetes mellitus, autoimmune, and other diseases. In patients with critical illnesses admitted to the Intensive Care Unit (ICU), serial examination of a panel of thyroid function tests, including T3 and rT3, is necessary to estimate the phase of the disease (whether acute, chronic, or recovery) and can be used to predict the risk of mortality during treatment.