Abstract AIMS The aim of the present study was to investigate the effects of combined training (CT) on total ghrelin and tumor necrosis factor-α (TNF-α) levels in obese middle-aged individuals. METHODS Twenty two obese middle-aged men (49.32 ± 5.74 years; Body mass index: 30.88 ± 1.64 kg/m²) were randomly assigned to a combined training group (CTG, n = 12) or a control group (CG, n = 10). The CT consisted of aerobic (50-85% of VO2peak) and resistance (6-10 RM) training performed three times per week, 60 min per session for 24 weeks. The anthropometric measurements, cardiorespiratory test (VO2peak), maximal strength assessment (1RM) and plasma concentrations of total ghrelin and TNF-α were determined before (Pre) and after 24 weeks (Post) of the experimental period. RESULTS Decreases were found in body fat percentage (Δ% -19.8) and waist circumference (Δ% -2.8) for CTG at the Post moment as compared to the Pre moment. In addition, the CTG demonstrated increases for VO2peak (Δ% 13.4) and for 1-RM of bench press (Δ% 78.1), leg press (Δ% 22.3) and arm curl (Δ% 19.3) at the Post moment as compared to the Pre moment. However, total ghrelin levels remained unchanged for CTG and CG after the experimental period, while TNF-α levels increased for CG (p ≤ 0.05). CONCLUSION the CT protocol performed was not effective in repairing total ghrelin levels and was not correlated with changes in the TNF-α; however, the exercise training was able to improve body composition and functional capabilities and contained the worsening of systemic inflammation associated to obesity.