Background: Gray matter brain structures, including deep nuclei and the cerebral cortex, are affected significantly and early in the course of multiple sclerosis and these changes may not be directly related to demyelinating white matter lesions. The hippocampus is an archicortical structure that is critical for memory functions and is especially sensitive to multiple insults including inflammation. However, in vivo quantification and longitudinal monitoring of neurodegenerative processes remain a challenging task. Thus, a need for reliable, inexpensive and easily assessable complementary surrogate markers for neuroaxonal degeneration still remains. Objective:We aimed to detect hippocampal volume loss in MS patients and to correlate such loss with cognitive dysfunction. we also aimed to investigate Optical coherence tomography (OCT) as a noninvasive tool used for measuring tissue at micrometer resolution as a marker of neurodegeneration and axonal loss.Subjects and methods: The study included 30 MS patients, who underwent full clinical neurological assessment, EDSS, cognitive functions assessment, hippocampal volume measurement and RNFLT detection of both optic discs and 20 age, sex and education matched normal healthy controls. Results:The mean hippocampal volume in MS patients was markedly reduced compared to controls. (p = 0.00). MS patients showed marked reduction in RNFLT of the superior and inferior quadrants on both sides and the left nasal quadrant, compared to control subjects, ( p = 0.00). A statistically significant negative correlation was found between mean volumes of the right and left hippocampi and mean EDSS (p = 0.01, 0.05 respectively). A statistically significant positive correlation was found between mean volume of the right hippocampus and mean RNFLT of the left nasal quadrant, (p = 0.03) and between mean volume of the left hippocampus and mean RNFLT of the left superior, left inferior and left nasal quadrants, (p = 0.00). Conclusion: MS patients showed evident reduction in hippocampal volumes and RNFLT compared to controls. RNFL thinning correlated well with hippocampal volume loss, supporting previous findings of other studies that RNFLT measured by OCT can be used as a surrogate marker of neuro-degeneration and axonal loss in MS patients.