Bio-catalytic processes have recently attracted attention as an interesting option for the degradation of persistent pollutants as they are capable to catalyze specific reactions at mild conditions and low environmental impact. In this work the potential to transform pharmaceutical micropollutants of a novel laccase from Pycnoporus sanguineus CS43 was compared to the commercial laccases Trametes versicolor and Myceliophtora thermophila. In the absence of redox mediators micropollutants were resistant to degradation, except for the antibiotic amoxicillin that was transformed by all laccases. The influence of natural and synthetic redox mediators (syringaldehyde, p-coumaric acid and ABTS) on the laccase oxidation system was investigated. Results showed the degradation of a complex mixture of pharmaceuticals is both compound and redox mediator dependent. Syringaldehyde resulted as the best redox mediator allowing the highest degradation yields of the antibiotics amoxicillin (80%), sulfamethoxazole (100%) and ciprofloxacin (40%) within 3 h treatment. Overall, commercial laccases showed better catalytic performance in comparison to P. sanguineus CS43 laccase especially in the presence of redox mediators. The successful transformation of pharmaceuticals by the combined action of different laccases and redox mediators demonstrate the potential of these systems for the removal of complex pollutant matrices.