Neoadjuvant therapy (NAT) for oesophageal cancer may reduce cardiopulmonary function, assessed by cardiopulmonary exercise testing (CPEX). Impaired cardiopulmonary function is associated with mortality following esophagectomy. We sought to assess the impact of NAT on cardiopulmonary function using CPEX and assessing the clinical relevance of any change in particular if changes were associated with post-operative morbidity. This was a prospective, cohort study of 40 patients in whom CPEX was performed before and after NAT. Thirty-eight patients underwent surgery and follow-up with perioperative outcomes measured. The primary variables derived from CPEX were the anaerobic threshold (AT) and peak oxygen uptake (V˙O2peak). There were significant reductions in the AT (pre-NAT: 12.4 ± 3.0 vs. post-NAT 10.6 ± 2.0 mL kg−1.min−1; p = 0.001). This reduction was also evident for V˙O2peak (pre-NAT: 16.6 ± 3.6 vs. post-NAT 14.9 ± 3.7 mL kg−1.min−1; p = 0.004). The relative reduction in V˙O2peak was greater in chemotherapy patients who developed any peri-operative morbidity (p = 0.04). For patients who underwent chemoradiotherapy, there was a significantly greater relative reduction in AT (p = 0.03) for those who encountered a respiratory complication. Cardiopulmonary function significantly declined as a result of NAT prior to oesophagectomy. The reduction in AT and V˙O2peak was similar in both the chemotherapy and chemoradiotherapy groups. •Neoadjuvant therapy reduces a patient's anaerobic threshold (AT) by 14.5%.•Neoadjuvant therapy reduces a patient's peak oxygen uptake (V˙O2peak) by 10.2%.•The reduction in cardiopulmonary function is similar with neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy.