The effects of synthetic wastewater that contained 20 mg/L Cu(II) on the removal of organic pollutants in a sequencing batch reactor were investigated. Results of continuous 20 mg/L Cu(II) exposure for 120 days demonstrated that the chemical oxygen demand (COD) removal efficiency decreased to 42% initially, followed by a subsequent gradual recovery, which peaked at 78% by day 97. Effluent volatile fatty acid (VFA) concentration contributed 67 to 89% of the influent COD in the experimental reactor, which indicated that the degradation of the organic substances ceased at the VFA production step. Meanwhile, the varieties of soluble microbial products (SMP) content and main components (protein, polysaccharide, and DNA) were discussed to reveal the response of activated sludge to the toxicity of 20 mg/L Cu(II). The determination of Cu(II) concentrations in extracellular polymeric substances (EPS) and SMP throughout the experiment indicated an inverse relationship between extracellular Cu(II) concentration and COD removal efficiency.