Abstract Background Sarcopenia, defined as the loss of muscle mass and function, is associated with a high risk of adverse outcomes in the cancer population. Radiologically defined sarcopenia has been linked to both short- and long-term outcomes after oesophagectomy for cancer. Neoadjuvant treatment plays a crucial role in the treatment of locally advanced oesophagogastric cancer. It is not fully clear whether patients with low muscle mass are more prone to sustaining acute chemotherapy toxicities during neoadjuvant chemotherapy (NAC) prior to oesophagectomy, especially when ECX or FLOT chemotherapy regimens are used. Methods Patients undergoing NAC and oesophagectomy between January 2016 and December 2022 had their skeletal muscle index analysed (SMI) at the time of initial staging. SMI was computed from staging CT scan slices as the lean muscle mass at the level of the third lumbar vertebra and the height of the patient. Patients were then divided into two categories depending on whether their NAC was completed fully (FLOT four cycles, ECX three cycles) or whether NAC treatment was incomplete. The Mann-Whitney U test was used to statistically test the hypothesis of any difference in SMI between these two groups. Results There were 208 patients included in this study. 109 patients had ECX and 90 patients had FLOT. Fourteen patients (6.7%) did not complete NAC treatment fully but progressed to oesophagectomy. The median (IQR) SMI of patients who did not complete NAC treatment was 46.54 cm2/m2 (43.40-51.32) compared to 50.87 cm2/m2 (45.88-57.33) for those who received all prescribed NAC cycles (p=0.026). Conclusion This study demonstrated that patients with higher SMI are better equipped to withstand the side effects of NAC and complete this treatment. It appears that strategies to improve sarcopenia before or during NAC are needed. Prehabilitation might be one of these strategies, and therefore, the effect of various prehabilitation regimens on sarcopenia needs to be further explored.