Purpose: Patients report a reduced preference for sweet and fatty foods after bariatric surgery. The mechanisms underlying this change in food preference are currently unknown. Methodology: Taste preference testing was performed in mice randomised to sleeve gastrectomy (SG) or sham surgery and followed by RNA sequencing and qPCR analysis of the small intestine. Immunohistochemical expression of neural c-Fos was also performed. A longitudinal clinical study assessed food preferences, weight loss, and metabolic markers after diet-induced weight loss, and SG or Roux-en-Y gastric bypass (RYGB). Results In mice, SG reduced 24-hour intake of glucose (mean SG 18.0g, mean sham 23.6g, p=0.016) and intralipid (mean SG 16.1g, mean sham 22.0g, p<0.001) but not standard chow (mean 2.8g both groups, p>0.05). SG mice were protected from progressive weight gain of up to 9% seen in the sham group. Transcriptomics revealed upregulation of the vagal afferent neurotransmitter cholecystokinin in the jejunum of SG mice. Expression of selected gut taste receptors was unchanged on qPCR. Increased neural activation was seen in reward regions but not taste regions in SG mice. Interim results from the clinical study suggest that bariatric surgery, but not diet-induced weight loss, leads to changes in food preferences. Conclusions SG reduces intake of sugars and fats, but not regular diet, in mice. This is associated with a neural activation pattern and intestinal genetic changes suggestive of altered vagal signalling and increased sensitivity to the rewarding-value of food. These changes broaden our understanding of how bariatric surgery facilitates sustained weight loss.