This work was conceived to investigate for the first time the effectiveness of the combined use of xylanase and laccase for the removal of hexenuronic acids (HexA) and lignin from sisal pulp fibres. To this end, xylanase (X) and laccase (L) treatments were used in an XLQPo sequence (where Q denotes a chelating stage and Po an oxygen-reinforced peroxide multi-step treatment) that was applied to pulp in order to obtain sisal fibres with a high cellulose content. The results of the XLQPo sequence were compared with those of an LQPo sequence. The L stage of both sequences was performed in the presence of either the natural compound sinapyl aldehyde (SLD) or the synthetic compound violuric acid (VA), employed as mediators, in order to compare their efficiency in aiding pulp bleaching and HexA removal. Changes in HexA content and the contributions of lignin and HexA to kappa number during each sequence were examined. The xylanase treatment was found to remove 47% of lignin, 15% of xylan and 27% of HexA from the initial pulp, whereas the laccase–VA system removed 28% of HexA and exhibited higher efficiency than the laccase–SLD system in reducing kappa number and increasing brightness. In any case, when the X treatment was applied, the sequence including laccase–SLD treatment resulted in the strongest delignification effect. The effluents from each stage of the bleaching sequences were analysed for COD, colour and toxicity, which peaked after the L stage and were significantly higher with SLD than with VA