BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition in urology characterized by chronic pain. The pathogenesis of CP/CPPS remains unclear. METHODS: We enrolled 45 eligible CP/CPPS patients and 45 healthy volunteers. We evaluated their resting-state fMRI data using a comprehensive set of parameters, such as Regional Homogeneity (ReHo) and Degree Centrality (DC), to detect brain abnormalities and identify potential correlates with the clinical manifestations of CP/CPPS. We further categorized the patients into subgroups according to their scores of NIH-CPSI to elucidate the brain changes associated with differing symptom severities. RESULTS: Profound alterations in brain function were observed in patients with CP/CPPS. These changes involved multiple brain regions identified by DC analysis, including the right anterior cingulate cortex (ACC), left inferior frontal opercular cortex, left amygdala, right middle frontal cortex, and bilateral insula. ReHo analysis revealed significant changes in the right thalamus, left inferior frontal triangular cortex, right superior temporal pole, left ACC, and right superior frontal cortex (cluster >20 voxels, GRF correction, < 0.05). Analysis using ReHo and DC revealed that brain alterations associated with varying symptom severities were localized in pain perception and modulation regions. Specifically, the DC values in the right ACC showed a linear correlation with the severity of symptoms measured by the NIH-CPSI (AUC = 0.9654, < 0.0001). CONCLUSION: In CP/CPPS, we first discovered differences in brain function among patients with varying degrees of severity. The brain alterations of DC in the right ACC might be a potential biomarker for diagnosing and assessing disease severity.