Abstract Background and Aims Primary hyperparathyroidism (HPT) is linked with several cognitive and affective disorders in the general population that tend to improve following parathyroidectomy. Most end- stage renal disease (ESRD) patients treated with maintenance haemodialysis (MHD) have 2ry/3ry HPT encompassing a broad range of serum intact parathyroid hormone (S. iPTH) values. They commonly suffer some degree of cognitive dysfunction (CODY) that impairs medication adherence and quality of life. This CODY results from the interplay of multiple factors, including HPT. However, relative hypoparathyroidism may as well cause CODY in the setting of adynamic bone disease and increased cerebrovascular calcification. Therefore, the relationship between S. iPTH and CODY in MHD patients needs to be clearly characterized across the whole spectrum of iPTH values. Method Seventy two stable ESRD patients (39 males, median age 50y) treated with thrice weekly low flux MHD for > 6 months underwent Montreal cognitive assessment- basic version (MoCA-B) and pre-dialysis assessment of S. iPTH, vitamin D3, alkaline phosphatase, urea, creatinine, calcium, phosphorus and haemoglobin (Hb). Results CODY, defined by a MoCA-B score < 24/30, occurred in 37/72 (51%) patients. MoCA-B score had a statistically significant positive correlation with Hb level. A quadratic inverted U-shaped curve provided the best estimate for the relation between S. iPTH and MoCA-B score (P = 0.019, Figure). Among patients in the highest S. iPTH tertile, S. iPTH has a statistically significant negative linear correlation with MoCA-B score (r = - 0.565, P = 0.004). This correlation was attenuated but persisted after controlling for Hb level (r = - 0.516, P = 0.012). Conclusion Anaemia and HPT are important contributors to the high prevalence of CODY in MHD patients. Both markedly high and relatively low (still above normal) S. iPTH levels are associated with lower MoCA-B scores, indicating a U- shaped relation between S. iPTH and CODY. Contrary to other populations, some degree of mild (permissible) HPT is most compatible with near normal cognitive function in MHD patients. Our results emphasize the recommendation of avoiding overzealous suppression of PTH secretion in these patients.