Low levels of dietary n-3 polyunsaturated fatty acids (PUFAs) are linked to anxiety and depression; however, the underlying mechanisms are unknown. Larrieu et al. showed that mice that were fed a diet deficient in n-3 PUFAs exhibited behavioural changes and neuronal atrophy patterns that resemble those of mice exposed to social defeat stress, a model of depression. These effects were linked to hypothalamic–pituitary–adrenal (HPA) axis hyperactivity and were reversed by n-3 PUFA supplementation. Thus, dietary n-3 PUFAs may be important in maintaining HPA axis function and preventing emotional impairment.