Abstract Kikuchi-Fujimoto disease (KFD) is usually self-limiting, but prolonged systemic symptoms often result in frequent hospital visits, long admission durations, or missed workdays. We investigated the role of fluorine-18 fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing KFD severity. We reviewed the records of 31 adult patients with pathologically confirmed KFD who underwent 18 F-FDG PET/CT between November 2007 and April 2018 at a tertiary-care referral hospital. Disease severity was assessed using criteria based on clinical manifestations of advanced KFD. Systemic activated lymph nodes and severity of splenic activation were determined using semi-quantitative and volumetric PET/CT parameters. The median of the mean splenic standardized uptake value (SUV mean ) was higher in patients with severe KFD than those with mild KFD (2.38 ± 1.18 vs. 1.79 ± 0.99, p  = 0.058). Patients with severe KFD had more systemically activated volume and glycolytic activity than those with mild KFD (total lesion glycolysis: 473.5 ± 504.4 vs. 201.6 ± 363.5, p  = 0.024). Multivariate logistic regression showed that myalgia (odds ratio OR 0.035; 95% confidence interval CI 0.001–0.792; p  = 0.035), total lymph node SUV max (cutoff 9.27; OR 24.734; 95% CI 1.323–462.407; p  = 0.032), and spleen SUV mean (cutoff 1.79; OR 37.770; 95% CI 1.769–806.583; p  = 0.020) were significantly associated with severe KFD. 18 F-FDG PET/CT could be useful in assessing KFD severity.