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The COVID-19 pandemic has exposed multiple structural flaws of global capitalism. These have been reproduced through the intensification of inequalities and reinforced through policy responses that have failed to protect the most vulnerable from the health and socio-economic impacts of COVID-19. The COVID-19 pandemic has also revealed the materiality of human activity and complex geographies of inequality. It has highlighted how inequalities embedded in relations of production, reproduction and global finance continue to perpetuate the divide between the Global North and South. Using an interdisciplinary political economy lens with a focus on the Global South, this Special Issue brings together contributions that explore the dynamics underpinning the intensification of inequalities during the pandemic and that analyse the initial policy responses to the COVID-19 crisis.