Background: This case-report characterized the respiratory, cardiovascular, and nutritional/gastrointestinal (GI) responses of a trained individual to a novel ultra-endurance exercise challenge. Case Presentation: A male athlete (age 45 years; V ˙ O2max 54.0 mL⋅kg-1⋅min-1) summited 100 mountains on foot in 25 consecutive days (all elevations >600 m). Measures: Laboratory measures of pulmonary function (spirometry, whole-body plethysmography, and single-breath rebreathe), respiratory muscle function (maximum static mouth-pressures), and cardiovascular structure and function (echocardiography, electrocardiography, large vessel ultrasound, and flow-mediated dilatation) were made at baseline and 48 h post-challenge. Dietary intake (four-day food diary), self-reported GI symptoms and plasma endotoxin concentrations were assessed at baseline, pre/post mid-point, pre/post end-point, and 48 h post-challenge. Results: The challenge was completed in a total exercise time of 142 h (5.3 ± 2.8 h⋅d-1), with a distance of 1141 km (42.3 ± 43.9 km⋅d-1), and energy expenditure of 80460 kcal (2980 ± 1451 kcal⋅d-1). Relative to baseline, there were post-challenge decreases in pulmonary capacities and expiratory flows (≤34%), maximum expiratory mouth-pressure (19%), and maximum voluntary ventilation (29%). Heart rate variability deteriorated, manifesting as a 48% decrease in the root mean square of successive differences and a 70% increase in the low-frequency/high-frequency ratio. Pre- to post-challenge endotoxin concentrations were elevated by 60%, with a maximum increase of 130% after a given stage, congruent with an increased frequency and severity of GI symptoms. Conclusion: The challenge resulted in pulmonary and autonomic dysfunction, endotoxaemia, and GI distress. The findings extend our understanding of the limits of physiological function and may inform medical best-practice for personnel supporting ultra-endurance events.