Anaemia continues to be a persistent concern among South African women of reproductive age (WRA), yet population specific information on its determinants remains sparse. We used baseline data from the Healthy Lives Trajectory Initiative a randomised trial (n = 480) to quantify factors associated with anaemia in Soweto, South Africa aged 18–25 years. We used multivariable logistic regression to describe associations with anaemia and used structural equation modelling to assess a theoretical model, which tested three categories socioeconomic status (household asset score, education level), nutritional factors (food security, leafy green vegetable and chicken and beef consumption, iron status and vitamin A status) and biodemographic factors (parity, age at start of menarche, HIV status, contraception use, anthropometry, and inflammation status). The multiple logistic regression showed that ID (OR: 2.62, 95% CI: 1.72, 3.98), iron deficiency erythropoiesis (IDE) (OR: 1.62, 95% CI: 1.07, 2.46), and elevated CRP (OR: 1.69, 95% CI: 1.04, 2.76), increased the odds of being anaemic. SEM analysis revealed Hb was directly and positively associated with adjusted ferritin (0.0031 per mg/dL; p≤0.001), and CRP (0.015 per mg/dL; p≤0.05), and directly and negatively associated with soluble transferrin receptor sTfR (-0.042 per mg/dL; p≤0.001). While contraception use had both a direct (0.34; p≤0.05) and indirect (0.11; p≤0.01) positive association with Hb. Additionally, chicken and beef consumption had a positive indirect association with Hb concentrations (0.15; p≤0.05) through adjusted ferritin. Iron deficiency was the main anaemia risk factor in this low resource setting. However, anaemia of inflammation is present. Therefore, we suggest that in our setting, WRA anaemia control programs that include interventions to reduce ID and inflammation should be tested.