Nuclear receptor coactivators (NCOAs), consisting of coactivators and corepressors, dramatically enhance the transcriptional activity of nuclear receptors. Hypoxia-inducible factor-1 α (HIF-1 α ) is a transcription factor that plays a major role under hypoxic conditions. This study was performed with the focus on the association of NCOAs with HIF-1 α in the serum of chronic kidney disease (CKD) patients. Sixty patients with stage 5 CKD and 30 healthy controls from The Second Affiliated Hospital of Shantou University Medical College, between March 21, 2019, and October 30, 2019, were recruited in this prospective cohort study. We analyzed the serum levels of NCOAs (NCOA1, NCOA2, and NCOA3), HIF-1 α , vascular endothelial growth factor (VEGF), etc. and assessed whether there was any relationship between these parameters and CKD disease. We found that circulating NCOA1 was positively associated with circulating NCOA2, NCOA3, and HIF-1 α . A positive correlation was also observed between NCOA2 and NCOA1, NCOA3, HIF-1 α , and VEGF. Furthermore, statistically significant correlations between NCOA3 and NCOA1, NCOA2, and HIF-1 α were observed. The serum levels of VEGF in the CKD group were higher than those of the healthy control group. Circulating NCOA1 and circulating NCOA2 were negatively associated with procalcitonin. In conclusion, there was an association between circulating NCOA1, NCOA2, NCOA3, and circulating HIF-1 α , and circulating VEGF was a risk factor for CKD disease. However, more studies should be performed to confirm this hypothesis., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Tianbiao Zhou et al.)