The widespread occurrence of micropollutants like the antibiotic sulfadimidine in the environment has become a growing concern. Compound-specific stable isotope analysis (CSIA) offers a powerful tool for tracking the fate of such pollutants, but its application is often limited by low sensitivity. To address this limitation, a large-scale solid-phase extraction method was developed to extract, enrich, and isolate sulfadimidine for delta 13C- and delta 34S-CSIA. Each step of the method was carefully evaluated, ensuring no detectable isotope artifacts. The limit of quantification was determined as 1.1 nmol of carbon and 1.2 nmol of sulfur directly injected on the column. Applied to groundwater samples from a contaminated site in Denmark, the method allowed for the analysis of concentrations as low as 0.17 mg/L, with a concentration factor of up to 10,000 used to enrich sulfadimidine. This is the first study to analyze delta 13C and delta 34S for sulfadimidine in aquifer water samples and highlights the potential of CSIA for tracking sulfadimidine transformations in contaminated water environments.