AbstractObjectiveSome patients regain weight to a variable extent from 1 year after Roux‐en‐Y gastric bypass surgery (RYGB), though rarely reaching preoperative values. The aim of the present study was to investigate whether, when, and to what extent metabolic remission occurs.MethodsFasting metabolite and lipid profiles were determined in blood plasma collected from a nonrandomized intervention study involving 148 patients before RYGB and at 2, 12, and 60 months post RYGB. Both short‐term and long‐term alterations in metabolism were assessed. Anthropometric and clinical variables were assessed at all study visits.ResultsThis study found that the vast majority of changes in metabolite levels occurred during the first 2 months post RYGB. Notably, thereafter the metabolome started to return toward the presurgical state. Consequently, a close‐to‐presurgical metabolome was observed at the time when patients reached their lowest weight and glucose level. Lipids with longer acyl chains and a higher degree of unsaturation were altered more dramatically compared with shorter and more saturated lipids, suggesting a systematic and reversible lipid remodeling.ConclusionsRemission of the metabolic state was observed prior to notable weight regain. Further and more long‐term studies are required to assess whether the extent of metabolic remission predicts future weight regain and glycemic deterioration.