To investigate the changes of spontaneous brain activity in patients with end-stage renal disease (ESRD) by combining three different resting state functional magnetic resonance low frequency amplitude algorithms, including amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and percent amplitude of fluctuation (PerAF), and to analyze the associations between spontaneous brain activity changes and clinical variables. The data of 31 ESRD patients treated with maintenance hemodialysis and 37 healthy volunteers in the Department of Nephrology and Renal Transplantation of the Affiliated Hospital of Qingdao University from August 2018 to December 2019 were retrospectively collected. The resting state functional magnetic resonance imaging (rs-fMRI) scan was performed to calculate the ALFF, fALFF, and PerAF values of the whole brain of the subjects in each group. Independent sample test was used for comparison between groups, and Pearson correlation analysis was used to investigate the correlation between spontaneous brain activity changes in brain regions with significant differences and clinical variables. Compared to healthy volunteers, patients with ESRD had decreased mean ALFF(mALFF) values of the right lingual gyrus, bilateral anterior precuneus, left inferior frontal gyrus, and right middle cingulate gyrus (FDR (false discovery rate) correction, all 0.01); and decreased mean PerAF (mPerAF) values of the bilateral anterior precuneus, bilateral posterior cingulate cortex, right calcarine fissure and surrounding cortex, bilateral inferior parietal lobule/temporoparietal junction (including bilateral angular gyrus, middle temporal gyrus, left supramarginal gyrus), and bilateral inferior frontal gyrus (FDR (false discovery rate) correction, all 0.01); but there was no significant difference in mean fALFF (mfALFF) value between the two groups. Correlation analysis showed that the mPerAF values of the right angular gyrus (=-0.509, =0.003) and the left supramarginal gyrus (=-0.405, =0.024) were negatively correlated with serum potassium concentration in ESRD patients, while mALFF values of the bilateral anterior precuneus (=0.058, =0.004) and mPerAF values of the left gyrus (=0.415, =0.020) were positively correlated with hemoglobin level. In ESRD patients, spontaneous brain activity was reduced in multiple brain regions, mainly located in default mode network(DMN), which might be the underlying pathophysiological mechanisms of their brain damage. Controlling serum potassium and hemoglobin levels was essential to prevent the progression of brain damage in ESRD patients.