Nesfatin-1 is a novel peptide with both central and peripheral anorexigenic regulatory properties. Besides its effects on food intake, few studies have suggested a possible role for this peptide in the pathogenesis of diabetes mellitus type 2. To compare serum levels of nesfatin-1 between healthy, normal-weight persons and three groups including healthy underweight, healthy obese and diabetic subjects. Prospective, case-control study, performed between January 2015 and January 2016. Fasting levels in serum nesfatin-1 were measured in 30 healthy, normal-weight individuals (controls), 30 healthy underweight persons, 30 healthy obese persons, and 30 patients with newly diagnosed diabetes type 2 using standard enzyme-linked immunosorbent assay (ELISA) kits. The mean serum nesfatin-1 level was significantly higher in controls (2.61 ng/mL) compared to that in obese (1.13 ng/mL) and diabetic (0.99 ng/mL) patients; and significantly lower than that in the underweight group (3.50 ng/mL). The obese and diabetic groups were comparable in this regard. No significant association was found between serum nesfatin-1 level and age, sex, or body mass index. Serum nesfatin-1 is possibly associated with weight-related abnormalities in otherwise healthy subjects and diabetes type 2. Obesity and diabetes type 2 may share a common pathologic point in this regard.