Background: Latent tuberculosis infection (LTBI) has been associated with increased immune activation. We assessed circulating concentrations of interferon-gamma in persons with LTBI. Methods: We used the 2011-2012 National Health Nutritional Examination Survey (NHANES) to identify adults with and without LTBI by QuantiFERON®-TB Gold In-Tube (QFT) results. Non-LTBI persons were 1:1 age-, gender-, and race-matched to LTBI persons using propensity scores. We compared the plasma concentrations of interferon-gamma measured from the unstim-ulated, negative control QFT tube between LTBI and non-LTBI persons. We used Mann-Whitney tests and ordered logistic regressions for comparisons. Results: There were 430 LTBI and 430 non-LTBI matched persons included in the analysis. LTBI was associated with higher circulating concentrations of interferon-gamma (median, 3 pg/mL; IQR, 2 – 5) compared to non-LTBI (median, 2.5 pg/mL; IQR, 1.5 – 3.5); P < 0.001. LTBI remained associated with higher interferon-gamma concentrations after adjusting for age, gender, race, diabetes, hypertension, tobacco use, HIV status, body mass index, lipid profile, and lympho-cyte count (odds ratio, 1.79, 95% CI, 1.26 – 2.53). Results remained similar when tuberculin skin testing defined LTBI. Conclusions: LTBI was associated with increased circulating interferon-gamma concentrations. Future studies are needed to further characterize immune activation in LTBI and its potential long-term consequences.