To fight infections, macrophages undergo a metabolic shift whereby increased glycolysis fuels antimicrobial inflammation and killing of pathogens. Here we demonstrate that the pathogen Candida albicans turns this metabolic reprogramming into an Achilles' heel for macrophages. During Candida-macrophage interactions intertwined metabolic shifts occur, with concomitant upregulation of glycolysis in both host and pathogen setting up glucose competition. Candida thrives on multiple carbon sources, but infected macrophages are metabolically trapped in glycolysis and depend on glucose for viability: Candida exploits this limitation by depleting glucose, triggering rapid macrophage death. Using pharmacological or genetic means to modulate glucose metabolism of host and/or pathogen, we show that Candida infection perturbs host glucose homeostasis in the murine candidemia model and demonstrate that glucose supplementation improves host outcomes. Our results support the importance of maintaining glucose homeostasis for immune cell survival during Candida challenge and for host survival in systemic infection. Display omitted •The macrophage Warburg effect becomes a liability during microbial challenge•In vitro, Candida competes for glucose, triggering massive macrophage death•In vivo, Candida infection promotes disruption of host glucose homeostasis•A glucose-rich diet improves host outcomes in systemic fungal infection Glucose is essential for innate immune cells to mount effective anti-fungal responses. Tucey et al. show that, for infected macrophages, dependence on glucose becomes their downfall: the human fungal pathogen Candida albicans rapidly consumes glucose, causing macrophages to die. In mice, maintaining host glucose homeostasis is important to prevent life-threatening fungal infection.