Aims: Energy density (ED) is known to influence body composition (BC). Indeed, consumption of high ED foods can increase body fat mass (BFM) and inflammatory markers. We sought to assess the mediatory role of high-sensitive-C-reactive protein (hs-CRP), transforming growth factorβ (TGF-beta), and plasminogen activator inhibitor-1 (PAI-1) on the relationship between ED and BC in women with overweight/ obesity.Methods: This was a cross-sectional study consisting of 391 women. Body composition (Bioelectrical Impedance Analysis) and a food frequency questionnaire (FFQ) was used to assess the BC and food intake of individuals. Blood samples and serum level of hs-CRP, PAI-1, and TGFβ were collected. ED per one gram of foods was calculated and divided to quartiles. Linear logistic regression was used to investigate the association between BC across quartiles of ED intake.Results: Total body water (TBW), fat free mass (FFM), visceral fat area (VFA), and fat free mass index (FFMI) appeared to be mediated by hs-CRP across ED quartiles. TBW, FFM with PAI-1, bone mineral content (BMC) with PAI-1 and TGF-beta, and skeletal lean mass (SLM) were inversely associated with hs-CRP, respectively. Fat trunk, TBW, BFM, FFM, SLM, waist circumference (WC), FFMI, and FMI were positively mediated by TGF-beta with increasing ED food intakes. Fat trunk, BFM, SLM, WC, FFMI and FMI were positively mediated by PAI-1.Conclusions: Most BC subcategories were positively associated with higher ED intake, mediated by increasing serum levels of PAI-1 and TGF-beta. Moreover, higher serum hs-CRP levels may be related to body fat and water alteration concomitant to a higher ED intake. How to cite this article: Bahrampour N, Mirzababaei A, Shiraseb F, Clark CCT, Mirzaei K. The mediatory role of inflammatory markers on the relationship between dietary energy density and body composition among obese and overweight adult women: A cross-sectional study. Int J Clin