Background: Profiles of amino acid metabolites (AAMs) have been linked to obesity and energy homeostasis. We investigated whether baseline obesity-related AAMs were associated with weight status in the early postoperative period after sleeve gastrectomy. Methods: In this prospective, single-arm, longitudinal study, 27 bariatric patients underwent sleeve gastrectomy. Twenty obesity-related AAMs were comprehensively quantified prior to surgery, and slow weight loss was defined as the lowest 40% of the percentage excess weight loss (%EWL) at three and six months postoperatively. Linear regression models were used to assess the association between baseline obesity-related AAMs and %EWL, and receiver operating characteristic curves were assessed. Results: Isoleucine and metabolites from the serotonin pathway were significantly associated with the %EWL at three and six months after sleeve gastrectomy. Among the metabolites identified to be significant in the regression analyses, serotonin (area under receiver operating characteristic curves (AUROC): 0.79, 95% confidence interval (CI): 0.59–0.97) and serotonin/5-hydroxytryptophan ratio (AUROC: 0.80, 95% CI: 0.58–1.00) showed superior performance in predicting slow weight loss six months after sleeve gastrectomy. Conclusions: Our findings underscore the importance of baseline AAM profiles, especially serotonin and serotonin/5-hydroxytryptophan ratio, in predicting slow weight loss in the early postoperative period after sleeve gastrectomy.