Introduction: Fragmented access to health and social care in low- and middle-income countries places the burden of care for the sick and elderly on informal carers (ICs).  Whilst literature highlights detrimental impacts of caring on ICs workforce participation in high-income countries, there is a scarcity of empirical evidence on this area in Sub-Saharan Africa. This paper investigates the relationship between employment and informal caring in South Africa and Zambia, with a specific focus on gender differences. Methods: Data were obtained from the baseline survey of the HPTN071 (PopART) study, a cluster-randomised controlled trial in 21 communities across South Africa and Zambia. Here, randomly selected adults (18-44 years) were asked about employment status, caring responsibilities, and other socio-demographic factors. Respondents’ employment status was modelled as a function of informal caring duties, age, sex, education, and wealth, using multiple logistic regression models. Results: The sample consisted of 5,881 individuals (71.7% female), including 376 ICs (72.3% female). Analysis showed being an IC was associated with increased employment odds for men (Odds Ratio (OR):1.732, 95% confidence intervals (CI):1.073-2.797). Whilst no association between employment and caring was seen for women, they experienced significantly lower employment odds than their male counterparts, in the total sample (OR:0.335, 95%CI:0.283-0.397) and the subsample of ICs (OR:0.238, 95%CI:0.188-0.298). Tertiary education increased employment odds, particularly for female carers ((OR: 8.798, 95%CI:4.985-15.526)). Conclusions: The Results highlight a major disparity between mens and womens employment odds – with women disadvantaged, irrespective of their caring status. This imbalance threatens achievement of sustainable development goal 5, gender equality, evidencing the economic barriers facing women in Sub-Saharan Africa. Incentivising retention of women at the highest levels of education is recommended as one route to dismantling this inequality. Whilst formalised support for ICs is also recommended, thorough cost-benefit analysis is needed to ensure productive resource allocation.