This study aimed to explore the efficacy of Tongdu Yupi Tiaoshen electric acupuncture on cognitive impairment in rats with chronic fatigue syndrome (CFS) and its impact on mitochondrial fission and mitophagy in the hippocampal CA1 region. Methods: A CFS cognitive impairment rat model was established using a chronic fatigue multifactorial compound stress method. The successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 10 rats in each, while another 10 healthy male SD rats served as the control group. During the treatment period, the control group was fed normally, the model group continued to receive modeling stimulation, and the electroacupuncture group received additional electroacupuncture treatment at the GV24 puncture GV20 and the GV14, with a continuous wave, frequency 10 Hz, 15 minutes per session per day, for a consecutive 28 days. The general condition and learning and memory abilities of rats in each group were evaluated using the General Conditions Semi-Quantitative Observation Scale and Morris water maze; transmission electron microscopy was used to observe the ultrastructure of mitochondria in the hippocampal CA1 region of rats in each group; Western Blot and RT-qPCR were used to detect the protein and mRNA expression levels of key molecules Pink1, Parkin, and Drp1 related to mitochondrial autophagy and mitochondrial fission in the hippocampal CA1 region of rats in each group. Results: After treatment, compared with the control group, the general condition score of the model group was increased (P< 0.05), the escape latency was prolonged (P<0.05), and the number of platform crossings was reduced (P<0.05); mitochondrial damage in the hippocampal CA1 region was increased, with swelling or shrinking in shape, lightened matrix with vacuolization, disappearance of cristae, incomplete outer membrane, and the appearance of autophagic bodies; the protein and mRNA expression levels of Pink1, Parkin, and Drp1 were decreased (P<0.05). After treatment, compared with the model group, the general condition score of the electroacupuncture group was decreased (P<0.05), the escape latency was shortened (P<0.05), and the number of platform crossings was increased (P<0.05); there were fewer damaged mitochondria and autophagic bodies in the hippocampal CA1 region, with mildly swollen shape, relatively clear inner cristae, cristae fracture but no disappearance of cristae protrusions, roughly intact outer membrane, and no significant change in matrix; the protein and mRNA expression levels of Pink1, Parkin, and Drp1 were upregulated (P<0.05). Conclusion: Tongdu Yupi Tiaoshen electric acupuncture has anti-fatigue and cognitive-improving effects, which may be related to the regulation of mitochondrial autophagy and mitochondrial fission function in CFS cognitive impairment rats.