Introduction <p>The clinical significance of gastric histopathological findings in laparoscopic sleeve gastrectomy (LSG) specimens remains debated. This study investigated whether gastric histopathology is associated with postoperative weight loss and metabolic outcomes following LSG, and whether any observed association is mediated through differences in postoperative weight loss.</p> Methods <p>This retrospective cohort study included 181 adult patients who underwent LSG between January 2022 and December 2024. Patients were classified into Group A (normal mucosa or inactive gastritis, <i>n</i> = 48) and Group B (pathological findings, <i>n</i> = 133). Weight loss, metabolic parameters, inflammatory markers, liver enzymes, and remission of associated medical problems were assessed at baseline, 6, and 12 months. Causal mediation analyses were performed to decompose the total effect of the pathology group into direct effects and indirect effects mediated through percentage total weight loss (%TWL).</p> Results <p>Group B achieved significantly lower %TWL at 12 months compared to Group A (31.8 ± 7.6% vs. 34.1 ± 5.8%, <i>p</i> = 0.030). Despite this difference, both groups demonstrated comparable improvements in all metabolic, inflammatory, and hepatic parameters, with no significant between-group differences. Causal mediation analysis revealed no clinically meaningful total or direct effects of gastric histopathology on any outcome at either time point. Subgroup analyses of H. pylori-positive and active gastritis patients separately confirmed no significant differences. Remission rates of associated medical problems for diabetes and hypertension were similar between groups.</p> Conclusion <p>Although patients with pathological gastric findings achieved modestly lower weight loss, this was not associated with differential metabolic, inflammatory, or hepatic outcomes following LSG, whether analyzed as a total effect or through causal mediation via weight loss.</p>