Background: Obesity is a major health problem in people with intellectual disabilities. It is also widely accepted that low-grade systemic inflammation associated to obesity plays a key role in the pathogenic mechanism of several disorders. Fortunately, physical activity has shown to improve inflammation in people with metabolic syndrome and type 2 diabetes. Accordingly, we assessed the influence of aerobic training on pro-inflammatory cytokines and acute phase proteins in women with Down syndrome. Methods: To achieve this outcome, 20 premenopausal obese young women with Down syndrome volunteered for this study. Eleven were randomly assigned to the intervention group and performed a 10-week aerobic training programme, three sessions per week, consisting of a warm-up then a 30-to 40-min treadmill exercise at a work intensity of 55-65% of peak heart rate followed by a cooling-down period. The control group included nine age-, sex- and body mass index-matched women with Down syndrome. Fat mass percentage and fat distribution were measured. Plasmatic levels of tumour necrosis factor (TNF)-a, interleukin (IL)-6 and fibrinogen were assessed by commercial enzyme-linked immunosorbent assay kits. C-reactive protein (CRP) was assessed by nephelometry. Results: Plasmatic levels of TNF-a (11.7?±?1.6 vs. 9.2?±?1.3?pg/ml; "P"?=?0.022), IL-6 (8.2?±?1.1 vs. 6.1?±?0.9?pg/ml; "P"?=?0.014) and high sensitive CRP (0.62?±?0.11 vs. 0.53?±?0.09?mg/dl; "P"?=?0.009) were significantly reduced in the intervention group. Further, significant correlations between plasmatic and anthropometric parameters were found. Conclusion: A 10-week training programme reduced pro-inflammatory cytokines and acute phase proteins in obese young women with Down syndrome. Long-term, well-conducted studies are still required to determine whether correction of this low-grade inflammation improves clinical outcomes of women with trisomy 21.