ObjectiveChronic kidney disease (CKD) is increasingly recognized as a risk factor for alterations in brain function. However, detecting early‐stage symptoms and structural changes remains challenging, potentially leading to delayed treatment. In our study, we aimed to investigate spontaneous brain activity changes in CKD patients using resting‐state functional magnetic resonance imaging (fMRI). Additionally, we explored the correlation between common biomarkers reflecting CKD severity and brain activity.MethodsWe recruited a cohort of 22 non–dialysis‐dependent CKD patients and 22 controls for resting‐state fMRI scans. Amplitude of low‐frequency fluctuations (ALFFs) and regional homogeneity (ReHo) were calculated to evaluate brain activity. Regression analysis was conducted to explore the correlations between biomarkers reflecting the severity of CKD and brain activity.ResultsCKD patients exhibited reduced z‐scored ALFF (zALFF) and mean ALFF (mALFF) in the bilateral putamen, right caudate nucleus, left anterior cingulate, and right precuneus. Changes in bilateral putamen were also found in smCohe‐ReHo and szCohe‐ReHo analyses. Urine albumin‐to‐creatinine ratio (UACR), urine protein‐to‐creatinine ratio (UPCR), and serum albumin levels were associated with attenuated putamen activity.ConclusionNon–dialysis‐dependent CKD patients had changes in zALFF, mALFF, smCohe‐ReHo, and szCohe‐ReHo values in specific brain regions, especially bilateral putamen. UACR, UPCR, and serum albumin levels are associated with putamen activity attenuation in rs‐fMRI.