The aim of this study was to evaluate the effect of microfiltration on the lycopene content and antioxidant capacity of watermelon juice using ceramic membranes with an average pore size of 0.1 μm and a permeable area of 0.022 m2. The influence of the tangential cross-flow velocity (4.3–6.4 m s−1) and temperature (23–37 °C) on the permeation flux, lycopene content and antioxidant capacity was evaluated. A 22 complete factorial experimental design was used. Increases in tangential cross-flow velocity and temperature had positive effects on permeation flux, with a maximum of 92.4 l h−1 m−2 achieved at 6.4 m s−1 and 30 °C. With regard to the lycopene content and antioxidant capacity, tangential cross-flow velocity was the only factor that exhibited significant effects on these responses. For the most concentrated extract, the lycopene concentration and antioxidant capacity were enhanced by 402.8% and 416.3%, respectively.