Obesity is associated with chronic inflammation characterized by increased levels of inflammatory cytokines, while exercise training reduces inflammation. Small EVs (30-150 nm) participate in cell-to-cell communication in part through miRNA post-transcriptional regulation of mRNA. Purpose: The current study examined if obesity and concurrent exercise training alter skeletal muscle: (1) EV miRNA content and (2) inflammatory signaling. Methods: Vastus lateralis biopsies were obtained from sedentary individuals with (OB) and without obesity (LN). Before and after seven days of concurrent aerobic and resistance training, muscle-derived small EV miRNA and whole muscle mRNA were measured. Results: Pathway analysis revealed that obesity alters small EV miRNA that target inflammatory (PEDF, Death Receptor, and Gαi) and growth pathways (Wnt/β-catenin, PTEN, PI3K/AKT, IGF-1). In addition, exercise training alters small EV miRNA in an anti-inflammatory manner targeting the IL-10, IL-8, toll-like receptor (TLR), and NF-κB signaling pathways. In whole muscle, IL-8 mRNA was reduced 50% and Jun mRNA was reduced 25% after exercise training consistent with the anti-inflammatory effects of exercise on skeletal muscle. Conclusions: Obesity and seven days of concurrent exercise training differentially alter skeletal muscle-derived small EV miRNA contents targeting inflammatory and anabolic pathways.