The microenvironment of pathological immunological niches is frequently characterized by chaotic and severe oxygen gradients that lead to areas of pathological hypoxia. Depending on the tissue, the determinants of pathological hypoxia are varied. In these niches, pathological hypoxia can drive immune cell dysfunction, which contributes to disease progression. This dysfunction may lead to the promotion of tumour growth, ischaemia, inflammation and a worse outcome in infection. PMN, polymorphonuclear neutrophil.