Methods, systems and apparatus for photo-processing of fluids, particularly complex fluids, such as blood products, pharmaceuticals, injectables and vaccines, are provided. The disclosed methods and systems employ non-laser light source(s) to generate monochromatic light energy, preferably in the range of 260 nm to 310 nm, for fluid treatment. Advantageous processing regimens and / or adjunct additives and / or agents may also be used to achieve desired and / or enhanced results, e.g., inactivation of pathogens, bacteria and / or viruses, modulation of immune response, and / or leukoreduction. Particularly preferred embodiments include specific wavelengths, novel temperature control systems and geometric / structural arrangements that provide enhanced processing results and / or efficiencies. The disclosed methods, systems and apparatus achieve desirable results in a broad range of diagnostic, therapeutic and treatment applications, and generally provide enhanced operating efficiencies and / or processing results in application modalities that employ a broad range of photo-activated and / or photo-responsive materials and / or compounds.