Abstract: Incorporating prior knowledge of respirometry estimation into multivariable principal analysis, a wastewater treatment process monitoring strategy is suggested. Respirometry measures the respiration rate of activated sludge, which concerns with the amount of oxygen consumed by microorganisms, and is estimated from the dissolved oxygen concentration of activated sludge reactors and some flow rates entering the system. Because the dissolved oxygen concentration and flow-meters which have quick response time and easy maintenance and steady operation are available at most industrial plants, the process monitoring strategy combining respirometry estimation have the advantage of fault detection rate and fault cause isolation and cost. When the new approach is demonstrated to monitor the typical abnormity of wastewater treatment plant such as storm event and toxin pulse entering Benchmark published by IAW, the sensitivity increase of some statistics indexes and fault detection in time are seen.