Water-coupled excimer lamp systems have been developed to inactivate microorganisms within complex, low–optical quality, fluids. Monochromatic lamps were selected to minimize UV-B and UV-C absorption within the carrier fluids while maximizing deposition within specific chemical targets. Fundamentals, system scaling and power supply design are discussed. This work used two large-surface area excimer lamps as intense sources of near monochromatic radiation at 308 and 282 nm. Data are presented for two distinct fluid systems: flow-through processing of large-volume metalworking fluids used in heavy industry and batch irradiation of human blood plasma and platelet suspensions used in transfusion medicine. In the first, a 200–600 L/min reactor is used to control bacterial concentrations within metalworking fluids used in large-scale metal machining processes. Control is defined as the maintenance of 103 to 104 CFU/mL in fluids that without treatment would have concentrations over 107 CFU/mL. The second is a batch process for viral inactivation in undiluted blood bank products. Samples of fresh frozen plasma and platelet suspensions were spiked with high titers of porcine parvovirus (PPV) and irradiated at 308 and 282 nm. Although both wavelengths were effective at reducing PPV levels, 308 nm light resulted in both higher rates of viral inactivation (greater than 6 log units) and lower rates of fluid degradation.