Background: Studies have suggested the potential roles of serum trace elements such as calcium and magnesium in the development of uterine fibroids. Aims: This study compared magnesium and calcium serum levels in reproductive-age women with and without uterine fibroids in Lagos, Southwest Nigeria. Methods: A comparative cross-sectional study of 194 parity-matched women with or without a sonographic diagnosis of uterine fibroids enrolled at a university teaching hospital in Lagos, Southwest Nigeria. Participants' sociodemographic, ultrasound, and anthropometric information as well as the estimated serum levels of calcium and magnesium were collected for statistical analyses. Results: This study found significant negative associations between low serum calcium levels and uterine fibroids (adjusted odds ratio= 0.06; 95% CI: 0.004, 0.958; p=0.047), uterine size (p=0.004), and the number of fibroid nodules (p=0.030). However, no significant association was observed between serum magnesium levels and uterine fibroids (p=0.341). Conclusion: The findings of this study suggest the promising role of calcium-rich diets and supplements in the prevention of uterine fibroids among Nigerian women. However, future longitudinal studies are required to further evaluate the potential role of these trace mineral elements in the development of uterine fibroids.