Life history theory seeks to understand how organisms distribute energy between physiological functions across the life course. A central assumption is that energy allocation involves “trade-offs” between competing functions relating to defence, maintenance, reproduction and growth. Constraints on human energy expenditure may produce trade-offs during energetic stress, affecting functions critical for homeostasis, survival and reproduction. While there is some evidence for binary trade-offs between two functions in humans, no studies have tested physiological resource prioritisation across multiple functions under energetic constraint. This study empirically assessed multiple human life history trade-offs and the proximate biological mechanisms underpinning them. We recruited 147 ultra-endurance athletes (107 male, 40 female) participating in four environmentally diverse multiday ultramarathons and one multiweek ocean rowing event. The severe energetic demands of these competitions provide a valuable opportunity to provoke and observe detectable trade-offs. We found evidence of trade-offs across multiple functions. Specifically, investment in (as indexed by immune biomarkers) was broadly prioritised relative to investment in storage, reproduction and maintenance. Our results enhance current understanding of the role of phenotypic plasticity in human adaptability and have implications for athlete health and performance as well as the emerging discipline of evolutionary public health.