BACKGROUND: Gastric cancer remains a major health concern worldwide, with locally advanced gastric cancer (LAGC) posing significant challenges due to frequent lymph node metastasis and poor prognosis. While curative gastrectomy with D2 lymph node dissection is the standard treatment, sarcopenia and perioperative skeletal muscle loss (SML) have emerged as critical prognostic factors. METHODS: We retrospectively analyzed 198 LAGC patients who underwent curative gastrectomy. Preoperative and postoperative sarcopenia were assessed via computed tomography (CT)-derived skeletal muscle index (SMI) at the L3 level. SML was defined based on sex-specific thresholds of SMI changes (%/30 days). Prognostic significance for overall survival (OS) and disease-free survival (DFS) was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: The prevalence of sarcopenia increased from 23.7% preoperatively to 33.3% postoperatively. Patients with significant muscle loss (SML) showed worse OS and DFS compared to non-SML patients (P <
0.05). SML was also associated with a higher incidence of Clavien-Dindo grade ≥ 3a complications (P <
0.05). Multivariate analysis identified preoperative sarcopenia (HR = 2.332, P = 0.001), postoperative sarcopenia (HR = 3.189, P = 0.011), and SML (HR = 11.231, P = 0.002) as independent risk factors for OS. Adjuvant chemotherapy significantly improved both OS (HR = 0.532, P = 0.015) and DFS (HR = 0.587, P = 0.041). CONCLUSIONS: Both preoperative sarcopenia and perioperative SML may negatively impact postoperative prognosis in LAGC patients, suggesting that perioperative evaluation of skeletal muscle mass may help identify high-risk surgical candidates for targeted interventions.