Due to the scarcity of potable water in many regions of the world, the demand for seawater as an alternative evaporative cooling medium in cooling towers (CTs) has increased significantly in recent years. Seawater make-up in CTs is deemed the most feasible because of its unlimited supply in the coastal areas of Gulf and Red Sea. However, the seawater CTs have higher challenges greatly mitigating their performances because it is an open system where biofouling and bio-corrosion occurring within the fillers and piping of recirculation systems. Their pilot-scale CTs were constructed to assess the performance of three types of oxidizing biocides or oxidants, namely chlorine, chlorine dioxide (ClO2) and ozone, for biofouling control. The test results showed that the addition of organic (5mg/L of methanol (MeOH)) increased the bacterial growth in CT basin. All oxidants were effective in keeping the microbial growth to the minimum. Oxidation increased the oxidation-reduction potential (ORP) level from 270 to 600mV. Total residual oxidant (TRO) was increased with oxidation but it was slightly increased with organic addition. Other parameters including pH, dissolved oxygen (DO), conductivity levels were not changed. However, higher formation of disinfection by-products (DBPs) was detected with chlorination and ozonation. This indicates the organic level should be limited in the oxidation for biofouling control in seawater CTs.