AIM: To assess the alterations in the resting-state function connections between the two cerebral hemispheres in patients with optic neuritis (ON) and healthy controls (HCs). METHODS: A total of 12 ON patients (six males and six females) and 12 HCs (six males and six females) who were highly matched for sex, age, and educational level were recruited. They underwent functional magnetic resonance imaging (fMRI), testing and brain activities were assessed using the degree centrality (DC) method. Correlation analysis between the mean DC values in specific brain areas and behavior performances was analyzed as well. Linear correlations between A anxiety scale (AS) and depression scale (DS) values and DC values in brain regions of patients with ON were also analyzed. RESULTS: The areas that showed a higher DC value in ON patients were the right angular gyrus and bilateral precuneus, while the left insula and left superior temporal gyrus (LSTG) were regions that presented a lower DC value in ON patients. A receiver operating characteristic (ROC) curve analysis confirmed the accuracy of the area under the curve (AUC) assessment. Linear analysis showed anxiety scale (AS) and depression scale (DS) values in the left insula were both negatively correlated with DC values, while best corrected visual acuity logMAR-R (BCVA logMAR-R) showed a negative correlation with DC in the LSTG. CONCLUSION: The study explores altered brain activities of specific regions in patients with ON. The results provide clues for revealing the underlying mechanism of ON development.