Background: Neuropeptide Y (NPY) is a sympathetic neurotransmitter with wide-ranging effects in various organ systems, from the central nervous system (CNS) to the cardiovascular system, the bone and the renal system. There is a strong association between serum concentration of NPY and deterioration of eGFR and proteinuria as suggested by recent studies, however, its real effect on chronic kidney disease (CKD) progression is uncertain. Objective: This study was conducted to assess the relationship between serum NPY and CKD progression. Materials and Methods: In this observational case-control study all participants were subjected to renal function tests and calculation of estimated glomerular filtration rate, urinary protein/creatinine ratio, serum NPY and pelviabdominal ultrasonography at baseline and repeated for the patients only after six months as follow up. Results: Serum NPY increased with a statistically significant difference in the patients group after six months follow up, the same as serum creatinine which increased significantly after six months and eGFR decreased with statistically significant difference. Also there was high statistically significant rise in the blood urea. There was no statistically significant difference rise in protein creatinine ratio after six months. The ROC curve determined the sensitivity and specificity of serum NPY as a marker of progression in CKD patients and the best cut off point to detect CKD status was calculated with NPY greater than 110 ng/L with sensitivity 100% and specificity 93.33%. Conclusion: Serum NPY could be a useful sensitive and specific marker that can be used as diagnostic and progression predictor for CKD.