There is evidence for the interest of (18)F-fluoro-deoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) in fever of unknown origin (FUO) clinical investigation. However, little and conflicting data exist about its place in the investigation procedure. The aim of this work was to evaluate the clinical value of (18)F-FDG-PET/CT in patients with FUO and identify patients who need early (18)F-FDG-PET/CT rather than a last-resort procedure. We performed a 2-year retrospective cohort study at the Nîmes University Hospital, France. A total of 79 patients (36 men, 43 women, mean age 54.0 ± 16.2 years) with FUO underwent (18)F-FDG-PET/CT. A final diagnosis was established in 61 (77.2 %) cases. Aetiologies of FUO were determined using (18)F-FDG-PET/CT findings in 45 (73.8 % of patients with diagnosis) cases. The sensibility and specificity value were 98 % and 87 %, respectively. The presence of adenopathy, low haemoglobin and increased C-reactive protein (CRP) were predictors of high-yield (18)F-FDG-PET/CT. (18)F-FDG-PET/CT may help to detect most causes of FUO. The predictors of high-yield (18)F-FDG-PET/CT found in this study can help identify patients likely to benefit from specific and early imaging techniques.