Background and Objectives: Our study aims to assess retinal nerve fiber layer (RNFL) thickness in patients affected by schizophrenia. Methods: Ten schizophrenic patients (mean age 39 +/- 13 years, best corrected visual acuity ≥ 20/20, refractive error between +/-2 diopters, and intraocular pressure <18 mmHg) were enrolled. They were compared with 10 age-matched controls. In all subjects, optic nerve head (ONH) measurements, peripapillary RNFL thickness, macular thickness and volume were measured by optical coherence tomography (OCT). Results: Schizophrenic patients showed an statistically significant reduction of the overall RNFL thickness (95+/-13 μm, range: 53-110) compared with those values observed in control eyes (103+/-8 μm, range: 88-119) (p = 0.047, Mann-Whitney U test). We also observed reduced peripapillary RNFL thickness in nasal quadrant in schizophrenic patients (75+/-17 μm, range: 41-111) when compared with controls (84+/-10 μm, range: 67-105) (p = 0.048, Mann-Whitney U test). The remaining peripapillary RNFL quadrants, macular thickness and volume did not reveal differences between both groups. No statistically significant differences were observed between the control group and schizophrenia patients with regard to ONH measurements, macular thickness and volume. Conclusions: Schizophrenia patients had a reduction of peripapillary RNFL thickness evaluated by OCT. To our knowledge, neither reduced RNFL thickness nor macular thickness and volume have been previously documented in patients diagnosed with schizophrenia. These findings suggest that neuronal degeneration could be present in the retina of schizophrenic patients as previously observed in neurodegenerative disorders.