A response surface methodology was used to determine the combined effect of HIPEF critical processing conditions on vitamin C, anthocyanins and antioxidant capacity of strawberry juice. Keeping constant the electric field strength at 35 kV/cm and the treatment time at 1000 μs, the treatments were set at frequencies from 50 to 250 Hz, pulse width from 1 to 7 μs using monopolar or bipolar mode. A second order response function covering the whole range of experimental conditions was obtained for each health-related compound. Strawberry juice antioxidant potential was affected linearly by frequency, pulse width and pulse polarity. The quadratic term of frequency and the combined effect of frequency and pulse width were also significant. HIPEF treatments conducted at 232 Hz with bipolar pulses of 1 μs led to strawberry juices with the greatest presence of health-related compounds. The evaluation of the HIPEF critical parameters influence on health-related compounds can contribute to achieve optimal processing conditions to obtain strawberry juices with high antioxidant potential.