Aims: Physical inactivity is associated with low-grade systemic inflammation and increased risk of chronic diseases. Beneficial effects of caffeine on adipocytes metabolism and its anti-inflammatory properties have been reported. This study aimed to evaluate the impact of 12 weeks of combined training and caffeine on plasma levels of inflammatory and anti-inflammatory indices in obese men. Methods & Materials: In a quasi-experimental trial, 44 obese men were purposefully and accessibly selected and assigned into four groups each 11 samples: 1) control, 2) combined (resistance-endurance) training, 3) caffeine, and 4) combined training with caffeine. The study subjects received 6 mg of caffeine per kilogram of body weight daily for 12 weeks. The combined training program was performed for 12 weeks, 3 sessions per week. The plasma levels of inflammatory (interleukin[IL]-1β) and anti-inflammatory (IL-10) indices were measured using an ELISA kit. The obtained data were analyzed by dependent t test, 1-way ANOVA, and Tukey post hoc test at the significant level of P<0.05. Findings: The results showed that 12 weeks of combined training, caffeine, and combined training-caffeine significantly reduced IL-1β levels and increased IL-10 in obese men at posttest compared to the pretest (P=0.001). Also, changes in IL-1β and IL-10 levels were greater in the combined training-caffeine group (P=0.001). Conclusion: Combined training with caffeine positively affects body composition and improves inflammatory and anti-inflammatory indices in obese people.