Abstract Background Elevation in serum inorganic iodine levels due to decreased urinary iodine excretion can result in thyroid enlargement, possibly contributing to nodular goiter and hypothyroidism in Chronic Renal Failure (CRF) patients. The mechanisms underlying thyroid dysfunction in Chronic Kidney Disease (CKD) remain unclear. Uremic toxins may interfere with thyroid hormone uptake and receptor binding, suggesting acquired thyroid hormone resistance in uremia Aim of the Work The main objective of this study is to determine the serum level of inorganic Iodine in End Stage Renal Disease Patients (ESRD). Also, as a main objective, is to correlate the findings with thyroid function tests. Patients and Methods This case-control study was conducted at Ain Shams University Hospitals, encompassing 100 ESRD patients on HD and 50 controls. Hypothyroidism prevalence was examined, with 9% among HD patients and 1% in the control group. Results Serum inorganic iodine levels were significantly higher in HD patients than controls (p < 0.001). Free T3 was lower, and TSH was higher in HD patients (p < 0.05). The incidence of thyroid nodules was markedly elevated in HD patients (p < 0.001). Conclusion Elevated inorganic iodine levels in most HD patients are associated with abnormal thyroid function tests and an increased frequency of thyroid nodules. Regular monitoring of iodine levels in HD patients, especially in the presence of thyroid gland clinical or chemical abnormalities, is recommended to prevent long-term complications.