Background: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are more common in women suggesting that female sex hormones play an important role in the pathogenesis and clinical aspects of these diseases. Objective: The aim of this study was to investigate the serum levels of estradiol, testosterone, dehydroepiandrosterone sulphate (DHEAS) and androstenedione in pos-tmenopausal SLE and SSc patients in compration with healthy women. The aim was also to examine the possible correlation sex hormones with diseases activity in SLE and SSc and correlation sex hormones with specific autoantibodies:antinuclear antibodies (ANA), anticentromeric antibodies (ACA) and DNA topoisomerase I antibodies (anti-Scl70), anti- double strand deoxyribonucleic acid antibodies (anti- dsDNA) and anti-Ro antibodies in SLE and SSc patients. Methods: Twenty-seven post-menopausal SSc patients, twenty-seven post-menopausal SLE patients and twenty-seven healhty women were enroled in the study. Serum levels of testosterone, DHEAS, androstenedione and estradiol were measured in all groups. Serum levels of ANA, ACA and anti-Scl70 were measured only in SSc patients, while in SLE patients were measured ANA, anti-dsDNA and anti-Ro antibodies. SSc activity was determined using EUSTAR (European Scleroderma Trial and Research) Systemic Sclerosis Activity Score, whereas in SLE patients was determined using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results: Serum levels of testosterone (0.64±0.56 nmol/L v. 1.64±1.02 nmol/l, p<0.001) and DHEAS (0.78±0.92μmol/L v. 2.00±1.08 μmol/L, p<0.001) were significantly lower in SLE patients compared to controls. There wasn't a significant difference in serum levels of androstendione (4.54±2.59 nmol/L v. 5.79±2.82 nmol/L, p=0.244) and estradiol (0.20±0.09 v. 0.16±0.06 nmol/L, p=0.250) between groups. Serum levels of testosterone negatively correlated with SLEDAI (r=-0.3809, p=0.049). Testosterone (r=-0.560, p=0.002), DHEAS (r=-0.563, p=0.002) and androstendione (r=-0.396, p=0.041) negatively correlated with ANA antibodies. Estradiol positivly correlated with anti-dsDNA antibodies (r=0.398, p=0.40). Testosterone (r=-0.453, p= 0.018) and DHEAS (r=-0.480, p=0.011) negatively correlated with anti- Ro antibodies. Serum levels of testosterone (0.80± 0.62 nmol/L v. 1.64±1.02 nmol/l, p<0.001), DHEAS (1.16±1.00 μmol/L v. 2.00±1.08 μmol/L, p=0.008) and androstenedione (3.26±3.08 nmol/L v. 5.79±2.82 nmol/L, p=0.004) were significantly lower in SSc patients compared to controls. There wasn't a significant difference in serum levels of estradiol between groups (0.18±0.84 v. 0.16±0.06 nmol/L, p=0.250). Serum levels of androstenedione negatively correlated with ACA antibodies (r=-0.434, p=0.024) while a positive correlation was found with anti-Scl70 antibodies (r=0.385, p=0.047). Testosterone levels positively correlated with anti-Scl70 antibodies (r=0.489, p=0.010). Conclusion: Circulating testosterone and DHEAS levels are decreased in post-menopausal SLE and SSc patients compared with healthy post-menopausal women. A positive correlation of androgens with anti-Scl70 antibodies and a negative correlation with ACA antibodies raise the question of the role of these hormones in the disease. A negative correlation of androgens with ANA and anti-Ro antibodies as well as SLEDAI confirms current knowledge about protective effect of these hormones in autoimmune diseases. Positive correlation of estrogenes with anti- dsDNA antibodies supports the findings of stimulating humoral immunity.