This study aimed to longitudinally assess CT body composition analyses in patients who experienced anastomotic leak post-oesophagectomy. Consecutive patients, between 1 January 2012 and 1 January 2022 were identified from a prospectively maintained database. Changes in computed tomography (CT) body composition at the third lumbar vertebral level (remote from the site of complication) were assessed across four time points where available: staging, pre-operative/post-neoadjuvant treatment, post-leak, and late follow-up. A total of 20 patients (median 65 years, 90% male) were included, with a total of 66 computed tomography (CT) scans analysed. Of these, 16 underwent neoadjuvant chemo(radio)therapy prior to oesophagectomy. Skeletal muscle index (SMI) was significantly reduced following neoadjuvant treatment (p < 0.001). Following the inflammatory response associated with surgery and anastomotic leak, a decrease in SMI (mean difference: −4.23 cm2/m2, p < 0.001) was noted. Estimates of intramuscular and subcutaneous adipose tissue quantity conversely increased (both p < 0.001). Skeletal muscle density fell (mean difference: −5.42 HU, p = 0.049) while visceral and subcutaneous fat density were higher following anastomotic leak. Thus, all tissues trended towards the radiodensity of water. Although tissue radiodensity and subcutaneous fat area normalised on late follow-up scans, skeletal muscle index remained below pre-treatment levels.