Aim: Efforts to tackle the global mental health crisis must be underpinned by a robust literature on the social determinants of mental health. Existing studies show consistent effects of economic hardship on mental health, emphasising the importance of basic needs, such as food. Outcomes are affected by family structure, with larger families and households with single adults experiencing greater budgetary strain. Our study aimed to investigate the extent to which effects of income on stress and well-being are mediated by food insecurity, whilst accounting for the effects of family size. Subject and methods: We surveyed a nationally representative sample (n = 1004) of UK adults, collecting key demographic information, plus data on food security (Household Food Security Survey Module Six-Item Short Form), perceived stress (four-item Perceived Stress Scale), and well-being (Office for National Statistics’ four-item personal well-being measure). Results: Our results demonstrated that meaningful portions of the effects of income on stress (44%) and well-being (37%) can be accounted for by food insecurity. We also found that 42% of the effect of family size on perceived stress could be accounted for by the increased food insecurity experienced by larger families. Conclusion: Our results add to a growing body of evidence suggesting that tackling economic hardship and ensuring the satisfaction of material needs would support improved mental health outcomes. Further, given that evidence demonstrates important impacts of stress on other factors such as obesity and cognition, we argue that tackling poverty and ensuring food security would also have physical health benefits.