Objectives To measure central macular thickness in Jordanian patients with sickle cell disease who did not have retinopathy and compare the findings with age- and sex-matched controls using spectral domain optical coherence tomography (SDOCT). Methods In this cross-sectional study, participants underwent visual acuity testing, slit-lamp bio-microscopy, dilated ophthalmoscopy, and SDOCT imaging to measure central macular thickness. Macular quadrant measurements and thickness difference indexes (TDIs) were compared between groups. Results Twenty eyes with sickle cell disease and 20 control eyes were enrolled. The median visual acuity in both groups was 20/20. The mean macular thickness was significantly lower in eyes with sickle cell disease than in matched controls (mean difference, 22.15 ± 6.44 µm). Peripheral quadrants were all significantly thinner in eyes with sickle cell disease, especially in superior and temporal quadrants. TDIs were lower in eyes with sickle cell disease than in control eyes. Conclusions Eyes with sickle cell disease that had no clinical evidence of retinopathy exhibited significantly lower central macular thickness in all quadrants, compared with eyes in age- and sex-matched controls. SDOCT is a non-invasive imaging modality that can detect preclinical changes in eyes with sickle cell disease and can be used to screen and monitor the disease process.