Background Away from home (AFH) meals are known to be energy-dense and of poor diet quality. Both direct and indirect exposure (e.g., neighborhood restaurant density) to AFH meals have been implicated as contributors to higher body weight and adverse health outcomes. Objective To examine the association of frequency of eating AFH and fast-food meals with biomarkers of chronic disease and dietary intake. Design This cross-sectional study used frequency of AFH and fast-food meal and biomarker data from the NHANES 2005-2010. Information on weekly frequency of AFH and fast-food meals was collected via questionnaire during the household interview. The metabolic biomarkers examined included BMI, serum cholesterol (total, HDL, and LDL), triglycerides, glycohemoglobin, and fasting glucose (n=8314, age ≥20, NHANES 2007-2010). Biomarkers of dietary exposure included serum concentrations of vitamins A, D, E, C, B-6, B-12, folate, and carotenoids (n=4162; 2005-2006). Multiple linear and logistic regression methods adjusted for complex survey methodology and covariates. Results American adults reported a mean of 3.9 (95% CI 3.7, 4.0) AFH and 1.8 (1.6, 1.9) fast-food meals/week. Over 50% of adults reported ≥3 AFH and >35% reported ≥2 fast-food meals/week. Mean BMI of more frequent AFH or fast-food meal reporters was higher (Ptrend≤0.0004). Serum concentrations of total, LDL, and HDL cholesterol were related inversely with frequency of AFH meals (P<0.05). Frequency of fast-food meals and serum HDL-cholesterol were also related inversely (P=0.0001). Serum concentrations of all examined micronutrients (except vitamin A and lycopene) declined with increasing frequency of AFH meals (P<0.05); women and ≥50 y olds were at higher risk. Conclusions Reporters of frequent AFH and fast-food meals had higher BMI and lower concentrations of HDL cholesterol; but profiles of other biomarkers did not indicate higher metabolic risk. However, the serum concentrations of nutrients with mostly plant foods as sources declined with increasing AFH meal frequency.