Aim To study the relationship between melatonin levels and Melatonin membrane receptor 1A ( MTNR1A ) SNP (rs13140012) in end-stage renal disease patients (ESRD) in Alexandria, Egypt on maintenance hemodialysis with or without atherosclerosis. Materials and methods 40 end-stage renal disease patients on regular hemodialysis were divided into 2 subgroups, one with (n = 20) and one without atherosclerosis (n = 20) and normal subjects (n = 40). Serum melatonin, carotid intimal medial thickness (CIMT) were measured. Melatonin membrane receptor 1A ( MTNR1A ) SNP (rs13140012) genotyping was done using 5'nuclease Allelic discrimination. Results Serum melatonin was significantly lower in ESRD patients [1.6 to 11.30 (pg/mL) with a median of 2.5] than the control group [20.50 to 56.40 (pg/mL) with a median of 35.20]. Serum melatonin was significantly lower in atherosclerotic patients subgroup [1.6–2.50 (pg/mL) with a median value of 2.30] than non-atherosclerotic patients subgroup [2.0–11.30 (pg/mL) with a median of 4.9]. No significant association was found between serum melatonin and ( MTNR1A ) SNP (rs13140012) (p = 0.633). Conclusion These results lead us to suggest that melatonin production is impaired in ESRD patients (included in this pilot study), and this impairment is more evident in atherosclerotic ESRD patients.