Background <p>Our study aims to compare Alpha-MSH (α-MSH) levels and their relationship with sleep state in cases with and without chronic kidney disease (CKD).</p> Material and Methods <p>We included CKD-diagnosed patients and a control group in this study. We assessed α-MSH, serum creatinine, and albumin levels in CKD-diagnosed patients and performed the Epworth sleepiness scale (ESS).</p> Results <p>A total of 155 people (56 controls, 84 CKD who did not need renal replacement therapy (CKD-without HD), and 15 under chronic hemodialysis (HD) therapy) were included in the study. ESS resulted in “sleepy” in 46.7% of HD, 33.3% in non-RRT CKD, and 19.6% in the control group. Sleepiness was statistically higher in the whole CKD (non-RRT and HD) group compared with the healthy group (<i>p</i> = 0.004). Pathologic ESS results had a positive correlation with the CKD stage and body mass index (BMI) in patients among the non-RRT CKD group. The most influential factors were BMI and eGFR. Considering all the patients, α -MSH results were highest in the control group and higher in the non-RRT group than in the HD group. Multivariate analysis revealed that the most significant factors were BMI and eGFR for pathologic ESS results.</p> Conclusions <p>α-MSH levels in patients who diagnosed with CKD were lower than in the healthy group. The anti-inflammatory and sleep functions of <i>α</i>-MSH must be researched extensively. CKD patients with low eGFR and high BMI are at risk for sleepiness. In this group, special evaluation should be made in terms of sleep disorders.</p> Trial registration <p>The research had done with following permissions in Türkiye.</p>