This paper presents a full-scale experience of sludge minimization by means of short contact time ozonation in a wastewater treatment plant (WWTP) mainly fed on textile wastewater. The WWTP performance over a 3-year operational data series was analysed and compared with a two-year operation with sludge ozonation. Lab-scale respirometric tests were also performed to characterize biomass activity upstream and downstream of the ozone contact reactor. Results suggest that sludge ozonation: (1) is capable of decreasing excess sludge production by 17%; (2) partially decreases both N removal, by lowering the denitrification capacity, and P removal, by reducing biomass synthesis; (3) increases the decay rate from the typical value of 0.62 d−1 to 1.3 d−1; (4) decreases the heterotrophic growth yield from the typical value of 0.67 to 0.58 gCOD/gCOD.