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The feasibility of an electro-Fenton process to treat tylosin (TYL), a non-biodegradable antibiotic, was examined in a discontinuous electrochemical cell with divided cathodic and anodic compartments. Only 15 min electrolysis was needed for total tylosin degradation using a carbon felt cathode and a platinum anode; while 6 h electrolysis was needed to achieve high oxidation and mineralization yields, 96 and 88 % respectively. Biodegradability improvement was shown since BOD₅/COD increased from 0 initially to 0.6 after 6 h electrolysis (for 100 mg L(-1) initial TYL). With the aim of combining electro-Fenton with a biological treatment, an oxidation time in the range 2 to 4 h has been however considered. Results of AOS (average oxidation state) and COD/TOC suggested that the pretreatment could be stopped after 2 h rather than 4 h; while in the same time, the increase of biodegradability between 2 and 4 h suggested that this latter duration seemed more appropriate. In order to conclude, biological cultures have been therefore carried out for various electrolysis times. TYL solutions electrolyzed during 2 and 4 h were then treated with activated sludge during 25 days, showing 57 and 67% total organic carbon (TOC) removal, respectively, namely 77 and 88% overall TOC removal if both processes were considered. Activated sludge cultures appeared, therefore, in agreement with the assessment made from the analysis of physico-chemical parameters (AOS and COD/TOC), since the gain in terms of mineralization expected from increasing electrolysis duration appeared too low to balance the additional energy consumption.