Resumen: It is difficult to guarantee the effectiveness of UV technology to reach 5 Log10 cycles of inactivation of Escherichia coli in a large amount of fruit juices with high absorption coefficients and turbidities, such as orange juice. The aim of this work was to overcome this limitation by combining UV light and mild temperatures. UV treatments were carried out in an equipment with eight individual annular thin film flow-through reactors connected sequentially and submerged in a thermostatic water bath. A treatment of 13.55 J/mL reached 0.25 ± 0.04, 0.41 ± 0.13, 0.84 ± 0.32, 0.96 ± 0.12, 2.57 ± 0.05, 5.41 ± 0.23, and more than 6 Log10 cycles of inactivation of E. coli STCC 4201 suspended in commercial sterilized orange juice at 25.0, 40.0, 50.0, 52.5, 55.0, 57.5, and 60.0 °C, respectively. The comparison of UV resistance at 25 °C with heat resistance at mild temperatures demonstrated a synergistic effect of both technologies applied simultaneously. The maximum synergistic lethal effect was reached at 55 °C (68.03%).