The seasonal variation of five selected multimetric indices for the determination of the Ecological Quality Status (EQS) of transitional waters was evaluated, as well as the indices' responses to an extreme drought event that occurred in 2005. The database used regards the Mondego River estuary, which was sampled from June 2003 to August 2006 on a monthly basis. Among the selected indices (EBI-Deegan et al. [Deegan, L., Finn, J.T., Ayvazlan, S.G., Ryder-Kieffer, C.A., Buonaccoesi, J., 1997. Development and validation of an Estuarine Biotic Integrity Index. Estuaries 30(3), 601-617], EDI-Borja et al. [Borja, A., Franco, J., Valencia, V., Bald, J., Muxika, I., Belzunce, M.J., Solaun, O., 2004. Implementation of the European Water Framework Directive from the Basque Country (northern Spain): a methodological approach. Marine Pollution Bulletin 48(3-4), 209-218], EFCI-Harrison and Whitfield [Harrison, T.D., Whitfield, A.K., 2004. A multi-metric fish index to assess the environmental condition of estuaries. Journal of Fish Biology 65, 683-710], EBI-Breine et al. [Breine, J.J., Maes, J., Quataert, P., Van den Bergh, E., Simoens, I., Van Thuyne, G., Belpaire, C., 2007. A fish-based assessment tool for the ecological quality of the brackish Scheldt estuary in Flanders (Belgium). Hydrobiologia 575, 141-159] and TFCI - Coates et al. [Coates, S., Waugh, A., Anwar, A., Robson, M., 2007. Efficacy of a multi-metric fish index as an analysis tool for the transitional fish component of the Water Framework Directive. Marine Pollution Bulletin 55, 225-240]), the EBI by Breine et al. (2007) was the only that evidenced clear interannual and seasonal variations. The EQS by the several indices ranged from "Low" to "High", depending on the index considered, evidencing the high level of mismatch between indices. The results are discussed in the scope of the EU Water Framework Directive, regarding monitoring strategies, application of indices and EQS assessment.