In this work, the degradation performance for the photocatalytic oxidation of eight micro-pollutants (amisulpride, benzotriazole, candesartan, carbamazepine, diclofenac, gabapentin, methlybenzotriazole, and metoprolol) within real secondary effluent was investigated using three different reactor designs. For all reactor types, the influence of irradiation power on its reaction rate and energetic efficiency was investigated. Flat cell and batch reactor showed almost similar substance specific degradation behavior. Within the immersion rotary body reactor, benzotriazole and methyl-benzotriazole showed a significantly lower degradation affinity. The flat cell reactor achieved the highest mean degradation rate, with half time values ranging from 5 to 64 min with a mean of 18 min, due to its high catalysts surface to hydraulic volume ratio. The EE/O values were calculated for all micro-pollutants as well as the mean degradation rate constant of each experimental step. The lowest substance specific energy per order (EE/O) values of 5 kWh/m3 were measured for benzotriazole within the batch reactor. The batch reactor also reached the lowest mean values (11.8–15.9 kWh/m3) followed by the flat cell reactor (21.0–37.0 kWh/m3) and immersion rotary body reactor (23.9–41.0 kWh/m3). Catalyst arrangement and irradiation power were identified as major influences on the energetic performance of the reactors. Low radiation intensities as well as the use of submerged catalyst arrangement allowed a reduction in energy demand by a factor of 3–4. A treatment according to existing treatment goals of wastewater treatment plants (80% total degradation) was achieved using the batch reactor with a calculated energy demand of 7000 Wh/m3.