Anaemia is a major driver of hyperlactatemia, but in lethal P. yoelii 17XL infection, additional hypoxia‐driven glycolytic and organ‐injury mechanisms exacerbate lactate accumulation. Combined anti‐malarial and transfusion therapy enhances recovery. TFF3 correlates with lactate and malaria severity, linking gut injury to systemic metabolic dysfunction in severe malaria. Here, TFF3 is linked to malaria.