It is difficult to guarantee the effectiveness of UV technology to reach 5Log10 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 13.55J/mL reached 0.250.04, 0.410.13, 0.840.32, 0.960.12, 2.570.05, 5.410.23, and more than 6Log10 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%). A UV light treatment (23.72J/mL) at 55 C (3.6min) of freshly squeezed orange juice allowed reaching more than 5Log10 cycles of inactivation of a E. coli cocktail (STCC 4201, STCC 471, ATCC 27325, ATCC 25922, and O157:H7 Chapman strain). The selected treatment did not affect the pH, acidity, Brix, and color, and decreased 16.45% ascorbic acid content and 63.96% the Pectinmethylesterase activity. The lethality of UV on Escherichia coli suspended in orange juice increased with temperature. The maximum synergistic effect of UV-H treatment was found at 55 C. A UV-H treatment of 23.72J/mL at 55.0 C inactivated more than 5Log10 cycles. The treatment did not affect the pH, acidity, Brix and color of orange juice. The UV-H decreased 16.45% ascorbic acid content and 81.27% the PME activity.