Cytokines are important factors of the immune system in autoimmune diseases such as multiple sclerosis (MS) in which damage caused by oxidants plays a major role in the pathology. Melatonin secreted by the pineal gland has recently been considered as an antioxidant. The purpose of this study was to determine the relationship between melatonin and cytokines in patients with MS. Thirty patients with MS and 30 healthy controls were selected. Serum levels of melatonin and cytokines, including interleukin-4, interferon-γ, and tumor necrosis factor alpha (TNF-α), were detected in all participants by the enzyme-linked immunosorbent assay (ELISA) method. There was a significant difference between patient and control groups in the levels of melatonin and TNF-α. Also, no significant correlation between the serum levels of melatonin and cytokines in both patient and control groups was seen. We concluded that decrease of melatonin and subsequent increase of pro-inflammatory cytokine, TNF-α, could be a factor in the inflammatory reactions in the pathologic process of MS.