Individuals' vulnerability to the risk of COVID-19 infection varies due to their health, socioeconomic, and living circumstances, which also affect the effectiveness of implementing non-pharmacological interventions (NPIs). In this study, we analysed socioeconomic-related inequalities in COVID-19 vulnerability using data from the nationally representative South African General Household Survey 2019. We developed a COVID-19 vulnerability index, which includes health and social risk factors for COVID-19 exposure and susceptibility. The concentration curve and concentration index were used to measure socioeconomic-related inequalities in COVID-19 vulnerability. Recentred influence function regression was then utilised to decompose factors that explain the socioeconomic-related inequalities in COVID-19 vulnerability. The concentration index estimates were all negative and highly significant (p < 0.01), indicating that vulnerability to COVID-19 was more concentrated among the poor. According to the decomposition analysis, higher income and education significantly (p < 0.01) positively impacted lowering socioeconomic-related COVID-19 vulnerability. Living in an urban region, being Black, and old all had significant (p < 0.01) positive impacts on increasing socioeconomic-related COVID-19 vulnerability. Our findings contribute to a better understanding of socially defined COVID-19-vulnerable populations in South Africa and the implications for future pandemic preparedness plans.