Background <p>Patients with end-stage renal disease (ESRD) who undergo long-term hemodialysis (HD) often suffer from fatigue and poor sleep quality. Although acupuncture is known to help regulate and enhance bodily functions, it remains uncertain whether laser acupuncture can benefit these patients. This double-blind, randomized, placebo-controlled trial aimed to evaluate the effects of laser acupuncture on reducing fatigue and improving sleep quality in hemodialysis patients. The study also considered time-varying dialysis and depressive symptoms.</p> Methods <p>Seventy-two patients were randomly assigned to either the laser acupuncture (LA) group or the control group. The LA group received acupuncture with a low-level laser at specific points: Hegu (LI4), Shenmen (HT7), Neiguan (PC6), Taixi (KI3), Zusanli (ST36), Yanglingquan (GB34), and Sanyinjiao (SP6). The control group received the same treatment without laser energy. Measurements were taken at baseline, Week 2, Week 4, and Week 6.</p> Results <p>Adjusted for HD and depression symptoms, the mixed linear model showed significant improvements in the LA group compared to the control group and baseline scores. Notable improvements were observed in fatigue visual analog scale scores, HD-related fatigue scale scores, recovery time after HD, and Pittsburgh sleep quality index at Week 2, Week 4, and Week 6 (<i>p</i> &lt; 0.05).</p> Conclusions <p>A six-week laser acupuncture treatment significantly improved fatigue and sleep quality in patients with ESRD on HD, regardless of dialysis timing and depressive symptoms. The treatment is non-invasive, safe, and short, making it a promising option for the post-dialysis period. Future research should evaluate the long-term effects of laser acupuncture on patients with HD, and involving more medical centers could strengthen the significance of this study’s results.</p> Implication for the profession and/or patient care <p>These findings provide valuable insights into the benefits of laser acupuncture for alleviating post-dialysis fatigue, shortening fatigue recovery time, and improving sleep quality in patients with ESRD undergoing HD. Starting in the second hour of the HD procedure, laser acupuncture can be applied to seven specific acupoints: LI4, HT7, PC6, KI3, ST36, GB34, and SP6. For the best results, it is recommended that laser acupuncture be performed for at least two weeks.</p> Trial registration <p>This clinical trial was registered in ClinicalTrials.gov with registration NCT06028685 (31/07/2023).</p>