Background: Obesity is a complex disease characterized by dysregulation in energy intake. The reward circuitry of the central nervous system is essential in food intake regulation. However, the effects of a short- and long-term fast on reward activity and subsequent caloric intake are not well understood. Methods: The neuroimaging food paradigm consisted of three pseudo-continuous arterial spin labeling (pCASL) MRI scans during an ad libitum nutrient drink (Ensure®) test (NDT) (drinking until maximal fullness). The first scan was performed before starting the NDT (Hunger) after a >12-hr (long-term) overnight fast or a 4-hr (short-term fast) after a 380-kcal standard breakfast, the second scan after reaching maximal fullness (Satiation), and the third scan 30-min after satiation (Satiety). Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated from the pCASL data. Brain regions of interest (right and left caudate, putamen, and nucleus accumbens NAc) were segmented from T2 volumes using Freesurfer (run_first_all) and used to mask CBF maps to determine the average CBF in each region. Changes in CBF were used as a proxy of neural activity. Results: A total of 43 patients with obesity (mean±SD age 37±10 years, body-mass index BMI 35.1±4.4kg/m2, 72% females) completed the study, 29 in the long-term fast and 14 in the short-term fast group. The long-term fast group consumed 1306±125 kcal in the NDT compared with 1125±301 kcal in the short-term fast (p=0.1). The short-term fast group had a significantly lower activity (CBF) in the left and right NAc, and left and right caudate nucleus during hunger, satiation, and satiety, and in the left and right putamen only at hunger. Conclusions: Recent (<4hrs) caloric intake decreases reward neural activity but not ad libitum energy intake in patients with obesity.