The combination of electro-oxidation and enzymatic oxidation was tested to evaluate the potency of this system to remove ciprofloxacin (CIP), a fluoroquinolone antibiotic, from water. For the electro-oxidation boron-doped diamond (BDD) and mixed metal oxides anodes were tested, at three current densities (4.42, 17.7 and 35.4 A/cm2). BDD anode at 35.4 A/cm2 exhibited the highest removal efficiency in the shortest time (>90 % removal in 6 min). For the enzymatic oxidation, laccase from Trametes versicolor was chosen. Laccase alone was not able to remove CIP; hence the influence of redox mediators was investigated. The addition of syringaldehyde (SA) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) resulted in enhanced CIP transformation. About 48.9±4.0 % of CIP remained after 4 h of treatment when SA-mediated laccase was applied and 87.8±6.6 % in the case of ABTS-mediated laccase. The coupling of enzymatic oxidation followed by electro-oxidation led to 73 % removal of the antibiotic. Additionally, the antimicrobial activity increased up to its original efficiency after the treatment. The combination of electro-oxidation followed by enzymatic oxidation led to 97-99 % removal of CIP. There was no antimicrobial activity of the solution after the treatment. The tests with wastewater confirmed the efficacy of the system to remove CIP from the complex matrix. Copyright © 2019 Elsevier B.V. All rights reserved.