BACKGROUND/AIMS Obesity and high salt intake are major risk factors for hypertension and cardiometabolic diseases. Obese individuals often consume more dietary salt. We aim to examine the neurophysiologic effects underlying obesity-related high salt intake. METHODS A multi-center, random-order, double-blind taste study, SATIETY-1, was conducted in the communities of four cities in China; and an interventional study was also performed in the local community of Chongqing, using brain positron emission tomography/computed tomography (PET/CT) scanning. RESULTS We showed that overweight/obese individuals were prone to consume a higher daily salt intake (2.0 g/day higher compared with normal weight individuals after multivariable adjustment, 95% CI, 1.2-2.8 g/day, P < 0.001), furthermore they exhibited reduced salt sensitivity and a higher salt preference. The altered salty taste and salty preference in the overweight/obese individuals was related to increased activity in brain regions that included the orbitofrontal cortex (OFC, r = 0.44, P= 0.01), insula (r = 0.38, P= 0.03), and parahippocampus (r = 0.37, P= 0.04). CONCLUSION Increased salt intake among overweight/obese individuals is associated with altered salt sensitivity and preference that related to the abnormal activity of gustatory cortex. This study provides insights for reducing salt intake by modifying neural processing of salty preference in obesity.