Introduction Obesity is associated with an imbalance in cytokine concentrations, characterizing a low-grade chronic inflammatory status. The cardiorespiratory fitness is an important parameter that influences this inflammatory status, being a powerful predictor of early mortality. The interdisciplinary therapy has emerged as an alternative to prevent and treat obesity by improving health parameters. The aim of this study was to examine the effect of an interdisciplinary therapy on inflammatory markers and cardiorespiratory fitness in obese adult women. Methods A total of twenty-eight (n = 28) adult women (age 43.3 ± 5.5 years and BMI 34.9 ± 3.1 kg/m 2 ) completed 20 weeks of interdisciplinary therapy involving physical exercise, nutritional and psychological support at Obesity Study Group in Federal University of Sao Paulo, Santos – Brazil. The cardiorespiratory fitness was measured through a maximal cycle-ergometer test. The inflammatory markers analyzed were leptin, TNF-α, MCP-1 and adiponectin. Results Improvement in leptin (Δ −25.7% p p 2 Max (Δ +15.4%, p = 0.001) and absolute VO 2 Max (Δ +10.8%, p = 0.001) were observed after the interdisciplinary therapy. In addition, a relevant negative correlation (r = −0.45, p = 0.021) was found between leptin level and cardiorespiratory fitness. Conclusion The interdisciplinary therapy showed a significant positive effect on leptin and MCP-1 levels, cardiorespiratory fitness and metabolic profile. The therapy also showed an important negative correlation between leptin and cardiorespiratory fitness. These results suggest that the proposed methodology can be effective to treat obesity by increasing aerobic fitness and reducing proinflammatory pathways. Clinical Trial Registration Number NCT02573688 .