Leptin, a peptide hormone, plays an essential role in the regulation of body weight, the endocrine function, reproduction, the immune response and inflammation. The immune system, in turn, modifies leptin’s production. Systemic lupus erythematosus (SLE) is an autoimmunological disease characterized by widespread inflammation with possible involvement of each body organ and system. In this study, we assessed serum leptin levels in SLE patients and the control group in search for correlations between leptin concentrations and other markers’ level, the activity of the disease, its duration, the age of the patients and their bone mineral density. Blood samples were collected from 30 SLE and 30 control group women. Each SLE patient was matched with one from the control for age (±1 year) and the body mass index (BMI; ±1). Serum leptin levels were determined using the DRG Leptin ELISA Kit. Serum leptin levels in SLE patients ranged from 1.8 to 66.3 ng/ml (median value 7.5), and in control group it was 8.8 ng/ml (0.7–39.2) (NS). In SLE, serum leptin levels (after the logarithmic transformation) correlated with BMI (r = 0.89, P < 0.0001), the age (r = 0.34, P < 0.01) and the patients’ disease duration (r = 0.59, P < 0.0005). Serum leptin levels in SLE patients with arthritis (P < 0.05) and central nervous system (CNS) involvement (P = 0.05) were significantly lower in comparison with serum leptin levels in SLE patients without arthritis and CNS involvement. No correlation was found between serum leptin levels and the T-score. In the control group, the logarithmic transformation of serum leptin levels positively correlated with BMI (r = 0.52, P < 0.05). No differences in serum leptin levels were shown between SLE patients and the control group. However, we found correlation between BMI and serum leptin levels in both groups. Furthermore, serum leptin levels in SLE patients with arthritis and CNS involvement were significantly lower in comparison with SLE patients without arthritis and CNS involvement, which suggests that active chronic inflammation may lower plasma leptin concentrations.