Metabolic adaptation is the lowering of basal metabolic rate (BMR) beyond what is predicted from changes in fat mass (FM) and fat-free mass (FFM) and may hamper weight-loss progression. It is unclear whether metabolic adaptation occurs following gastric bypass surgery (GBP) and if it persists. The aim of this study was to evaluate the reduction in BMR that is not explained by changes in body composition in patients following GBP compared to a weight-stable comparator group. Thirty-one patients [77.4% female; mean BMI 45.5(SD 7.0) kg/m2; age 47.4(11.6)y] who underwent GBP, and 32 time-matched comparators [50% female; BMI 27.2(4.6) kg/m2; age 41.8(13.6)y) were evaluated at 1-month pre-surgery, 3-, 12- and 24-months post-surgery. BMR was measured under standardised residential conditions using indirect calorimetry and body composition using DXA. Linear regression analyses assessed metabolic adaptation post-surgery. After surgery, patients lost a quarter of their body weight [-25.6%(1.8%); p < 0.0001] consisting mainly of FM (4:1 FM to FFM loss ratio) at 24-months post-surgery. Absolute BMR (MJ/d) reduced by 25.7% at 24-months post-surgery with values becoming similar to the comparator group from 3-months post-surgery. Positive associations were observed between changes in BMR and changes in FFM and FM (P < 0.03). Metabolic adaptation was present in patients during the 1) rapid weight loss phase (6.9 kg/month at 3-months post-surgery) (p = 0.011), 2) slower weight loss phase (1.6 kg/month from 3 to 12-months post-surgery) (p < 0.0001), and, 3) weight maintenance phase (24-months post-surgery) (p = 0.00073). However, the degree of metabolic adaptation observed in GBP patients was similar to the weight-stable comparator group (no metabolic adaptation) from 12-months post-surgery onwards (3-months; p = 0.01, 12-months; p = 0.26, 24-months post-surgery; p = 0.70). These results suggest that there is a potential biological mechanism of surgery that attenuates the expected postoperative downregulation in BMR thus helping GBP patients maintain weight loss.