Consuming adequate dietary fiber is a promising strategy for reducing systemic inflammation. The objective was to evaluate relationships between dietary fiber intake, markers of metabolic endotoxemia, and systemic inflammation in adults. This was a cross-sectional study of 129 healthy participants (age 33.6 ± 6.1 yr, BMI 30.5 ± 6.9 kg/m2). Dietary fiber intake was assessed by food frequency questionnaire. Adiposity was measured using dual-energy X-ray absorptiometry (DXA). Fecal short-chain fatty acids (SCFA) were quantified using gas chromatography-mass spectrometry. Fecal microbiota sequence data (V4 region, 16S rRNA gene) were analyzed using DADA2 and QIIME2. Inflammatory cytokines were assessed with enzyme-linked immunosorbent assays; flow cytometry was conducted for monocyte surface marker quantification. Bivariate correlations and generalized step-wise linear modeling were used for statistical analyses. Plasma C-reactive protein (CRP) and interleukin (IL)-6 concentrations were positively related to whole body (CRP r = 0.45, P = <0.0001; IL-6 r = 0.34, P = 0.0002) and visceral adiposity (CRP r = 0.33, P = 0.0003; IL-6 r = 0.38, P = 0.0002). Plasma lipopolysaccharide-binding protein (LBP) concentrations were inversely related to dietary fiber intake (r = -0.22, P = 0.03) and fecal SCFA (acetate r = -0.25, P = 0.01; propionate r = -0.28, P = 0.003; butyrate r = -0.23, P = 0.02). Whole body adiposity, dietary fiber, and fecal SCFA were the most predictive of plasma LBS-BP concentrations. Novel findings included associations between dietary fiber intake, the gastrointestinal microbiota, and systemic inflammation.NEW & NOTEWORTHY Dietary fiber intake may reduce the inflammation associated with obesity and metabolic disease. Our cross-sectional analysis revealed that dietary fiber intake and fecal short-chain fatty acids are inversely associated with lipopolysaccharide-binding protein, a marker of systemic inflammation. In addition, plasma interleukin-6 and C-reactive protein were positively related to markers of adiposity.