Leptin association with Multiple sclerosis (MS) pathogenesis and MS related clinical characteristics is inconsistent. Here, we investigated whether two common variants in leptin (LEP) and leptin receptor (LEPR) genes influence MS risk and leptin levels in MS patients.In a case-control study including 169 MS patients and 100 controls we examined the association of leptin in MS. Blood samples were used for DNA extraction and plasma retrieval. Taqman genotyping assays were used for LEP rs7799039 and LEPR rs1137101 genotyping, and enzyme-linked immunosorbent assay for plasma leptin level.Leptin levels were significantly lower in MS patients compared to controls (β = 0.157, 95%CI: 0.033-0.26, p = 0.012). LEP rs7799039AA associated with MS risk (OR: 2.52; 95%CI: 1.35-4.67, p = 0.003). None of the assessed markers associated with MS disability, severity or response to treatment.LEP rs7799039AA is a risk factor for MS in our Kuwaiti population, and leptin levels are lower in MS patients compared to healthy controls. Our findings suggest future studies must consider all factors influencing leptin levels to resolve its controversial involvement in MS pathogenesis or progression.