Chronic kidney disease (CKD) and dementia are common morbidities of elders. Serum cystatin C has been suggested to be an ideal marker for kidney function. The current study aimed to detect the serum levels of cystatin C in CKD patients and to correlate these levels to cognitive performance. The study involved 90 subjects aged 65 years and more, divided into two groups: Group 1: 60 patients with CKD, and Group 2: 30 control participants. Exclusion criteria included cardiac failure, hepatic failure, thyroid diseases, dialysis for more than one month, polycystic kidney disease, organ transplantation, and immunosuppressive therapy within the past six months. All participants had routine laboratory workup, serum cystatin C using enzyme-linked immunosorbent assay kits, and cognitive assessment using mini-mental state examination (MMSE). Serum cystatin level was significantly high in CKD patients while MMSE scores were significantly lower in CKD patients. A high significant negative correlation was found between serum cystatin C levels and both degree of cognitive impairment and glomerular filtration rate (GFR). Also, a significant positive correlation was found between the degree of cognitive impairment and GFR levels. Serum cystatin levels are significantly associated with cognitive impairment in CKD patients, and this correlation becomes more evident with the worsening of CKD stages. That may help in better understanding of the pathogenesis of dementia in CKD patients with the emergence of therapeutic options depending on these data.