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Background: Abnormal functional connectivity (FC) in the brain has been observed in schizophrenia patients. However, studies on FC between homotopic brain regions are limited, and the results of these studies are inconsistent. The aim of this study was to compare homotopic connectivity between first-episode schizophrenia (FES) patients and healthy subjects and assess its correlation with clinical symptoms. Methods: Thirty-one FES patients and thirty-three healthy controls (HC) were included in the study. The voxel-mirrored homotopic connectivity (VMHC) method of resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyse the changes in homotopic connectivity between the two groups. The 5-factor PANSS model was used to quantitatively evaluate the severity of symptoms in FES patients. Partial correlation analysis was used to assess the correlation between homotopic connectivity changes and clinical symptoms. Results: Compared to those in the HC group, VMHC values were decreased in the paracentral lobule (PL), thalamus, and superior temporal gyrus (STG) in the FES group (P