Pathogenic bacteria (as indicated by Escherichia coli) in combined sewer overflow (CSO) are a threat to public health. Techniques are needed to disinfect CSO before discharge into natural water bodies. In this work, disinfection of CSO by ultrasonication and electrochemical (EC) processes is examined. Ultrasonic disinfection performances were found to negatively correlate with ratios of initial turbidity to initial E. coli concentrations. Existence of a critical ultrasonic power density was observed beyond which no further improvement in ultrasonic disinfection was available. Nano-scale TiO2 was found to improve ultrasonic disinfection at high dosages and protect E. coli at low dosages. EC treatment was found to disinfect CSO samples cost-effectively and produced a residual disinfection effect. This work discovered the protection of Escherichia coli by suspended solids from ultrasonication and demonstrated that the EC technique has the potential for in-situ CSO disinfection