We report a noble optical sensing method to diagnose seed abnormalities using optical coherence tomography (OCT). Melon seeds infected with Cucumber green mottle mosaic virus (CGMMV) were scanned by OCT. The cross-sectional sensed area of the abnormal seeds showed an additional subsurface layer under the surface which is not found in normal seeds. The presence of CGMMV in the sample was examined by a blind test (n = 140) and compared by the reverse transcription-polymerase chain reaction. The abnormal layers (n = 40) were quantitatively investigated using A-scan sensing analysis and statistical method. By utilizing 3D OCT image reconstruction, we confirmed the distinctive layers on the whole seeds. These results show that OCT with the proposed data processing method can systemically pick up morphological modification induced by viral infection in seeds, and, furthermore, OCT can play an important role in automatic screening of viral infections in seeds.