Objective: Sleep quality(SQ) can be steady decline in the of breast cancer patients after treatment. The aim of this study was to assess the SQ of breast cancer patients treated with Cyclin-dependent kinase(CDK) 4–6 inhibitor plus endocrine therapy(ET). Metarial and Methods: The data were collected from three different cancer centers. Eighty consecutive patients were included in this study. The Pittsburg Sleep Quality Index(PSQI) was employed for the assessment of the SQ in metastatic breast cancer patients after receiving treatment with CDK4–6 inhibitors plus ET for at least three months. Results: The PSQI scores revealed that 68.8% of patients treated with CDK4–6 plus ET have poor SQ. The mean score of the PSQI was 8 (ranging from 1-17). Univariate analysis was employed, revealing a significantly higher sleep latency (p= 0.024), sleep disturbance (p= 0.011), and daytime dysfunction (p= 0.012) in patients receiving letrozole as compared to patients treated with Fulvestrant. Similarly, the mean score of the PSQI was also higher in letrozole-treated patients in comparison with Fulvestrant- treated patients (p= 0.042). The multivariate analysis revealed a significantly higher rate of daytime dysfunction in letrozole-treated patients as compared to Fulvestrant-treated patients (The odds ratio was 0.51, 95% confidence interval, 0.30 to 0.86; p=0.008). In addition, no significant difference was observed in the sleep quality of patients receiving either Ribociclib or Palbociclib. Conclusion: The study evidently shows worsening of SQ in patients receiving letrozole in comparison with patients receiving Fulvestrant. CDK4–6 inhibitors have a similar effect on SQ.