Background: New findings on adipose tissue physiology and obesity-associated inflammation status suggest that modification of the adipokine level can be relevant for the long-term prevention of obesity-associated chronic disease. Objectives: The scope of the present study was to investigate the effectiveness of physical exercise in reducing the systemic inflammation related to obesity in children. Methods: We conducted a systematic review with meta-analysis of controlled randomized trials, identified through electronic database search, which investigated the effect of physical exercise, without concomitant dietary intervention, on adiponectin, leptin, and/ or other inflammatory markers in children up to age 18 years with a body mass index greater than the 95th percentile for age and sex. Results: Seven trials were included in the meta-analysis, with a total of 250 participants. Compared with the control group without any lifestyle modification, the physical exercise resulted in a reduction in leptin [standardized mean difference (SMD) -1.13; 95% confidence interval (95%CI): -1.89 to -0.37; I 2 = 79.9%] and interleukin-6 (SMD -0.84; 95%CI: -1.45 to -0.23, I 2 = 0.9%) and an increase in adiponectin plasma concentration (SMD 0.69; 95%CI: 0.02–1.35; I 2 = 74.3%). Conclusions: These results indicate that physical exercise improved the inflammatory state in children with obesity. It is unclear whether this effect can reduce the risk of cardiovascular and metabolic disease in adulthood. Clinical trials with a uniform intervention protocol and outcome measurements are required to put our knowledge on adipose tissue biology into a clinical perspective.