Zinc (Zn) is known to interact with lead (Pb) and cadmium (Cd) reversing their toxicity and reducing their concentrations. However, lactating women are at high risk of developing Zn deficiency, which may result in Pb and Cd intoxication or increased exposure of breast-fed infants to Pb and Cd from breast milk. The aim of this study was to determine Zn, Pb, and Cd concentrations and examine their relationship in serum and breast milk of lactating women in Ibadan, Nigeria. Ninety-two lactating women were recruited into this study. Anthropometric measurements were assessed by standard methods while serum and breast milk concentrations of Zn, Pb, and Cd were assessed by atomic absorption spectrophotometry. Data analyzed statistically by Student's t test, Pearson's correlation coefficient, and a multiple regression model were significant at p < 0.05. Zn deficiency was observed in 12 (17.1%) of lactating women. Breast milk levels of Zn, Pb, and Cd were significantly higher than their levels in serum, whereas the ratios Zn:Pb and Zn:Cd in milk were significantly less than serum ratios. Significant negative correlation was observed between milk Pb and serum Zn:Pb while milk Cd correlated positively with milk Zn. Significant positive correlations were observed between serum Zn and serum Zn:Pb, serum Zn and serum Zn:Cd, as well as serum Zn:Cd and serum Zn:Pb. Serum Cd and serum Zn were significantly negatively related. Significant negative correlations between serum Pb and serum Zn:Pb as well as milk Zn:Pb. Serum Cd and serum Zn:Pb as well as serum Zn:Cd correlated negatively. Milk Cd and Zn/Cd positively related with milk Pb while milk Zn was a negatively related with milk Pb in a multiple regression model ( R = 0.333; p = 0.023). Breast milk may be contaminated by toxic metals. However, Zn supplementation in deficient mothers may protect maternal and infant health.