The performance of a two-stage process combining electro-coagulation (EC) and electro-oxidation (EO) was studied for the treatment of domestic wastewater (DWW) loaded with organic matter. The process was firstly evaluated in terms of its capability of simultaneously producing an oxidant and a coagulant agents using aluminum (Al) (or iron (Fe)) as bipolar and sacrificial electrodes, whereas graphite (Gr) electrodes were used as monopolar electrodes. Relatively high concentrations of chlorine (9.6 mg/min A) and Al (20-40 mg Al/L) or Fe (40-60 mg Fe/L) were produced. Subsequently, the factorial and central composite design methodologies were successively employed to define the optimal operating conditions for total chemical oxygen demand (COD) removal from DWW. Current intensity and treatment time were found to be very meaningful for chemical oxygen demand removal. The effect of these two main factors was around 90% on the investigated response, whereas the type of sacrificial electrode and the other interaction effects represent only 10%. The treatment using aluminum electrode and a current intensity imposed of 0.7 A during 39 min was found to be the optimal conditions in terms of cost/effectiveness. Under these conditions, 78% of COD removal can be obtained for a total cost of 0.78 US $/m(3).