AIM: To observe the morphological changes of corneal subbasal nerve (SBN) plexus in patients with Sj?gren syndrome (SS) by in vivo confocal microscopy (IVCM) study and analyze its correlation with clinical symptoms. METHODS: We collected 22 cases (44 eyes) patients with SS (observation group) and 22 cases (44 eyes) healthy people with the same age (control group) for observation of central corneal SBN fibers diameter, number of beads, and tortuosity, and recorded tear film break up time (BUT), Schirmer’s I test (SIT), tear meniscus height (TMH), dendritic cell (DC) density, the results were applied to perform statistical analysis. RESULTS: Under IVCM observation, the diameter of corneal SBN fibers in the observation group became thinner, the number of beads and the degree of nerve fiber tortuosity were increased compared with the control group, and the difference was statistically significant (P<0.05). Pearson correlation analysis: the diameter of corneal SBN fibers in the observation group was significantly correlated with BUT (r=0.472, P<0.01), SIT (r=0.562, P<0.01), TMH (r=0.246, P=0.02) and DC density (r=-0.636, P<0.01). The number of nerve fiber beads was correlated with BUT (r= -0.621, P<0.01), SIT (r=-0.688, P<0.01), TMH (r=-0.438, P<0.01) and DC density (r=0.528, P<0.01). There was a significant correlation between nerve fiber tortuosity and BUT (r=-0.634, P<0.01), SIT (r=-0.713, P<0.01), TMH (r= -0.384, P<0.01) and DC density (r=0.604, P<0.01). CONCLUSION: IVCM can effectively observe the morphology of corneal nerve plexus. In SS patients, the diameter of corneal SBN fibers becomes thinner, the number of beads increases, and the tortuosity of nerve fiber increases. Moreover, the degree of nerve fiber lesions is correlated with the severity of dry eye clinical symptoms.