Enterococcus faecalis inactivation was carried out by solar photo-Fenton at initial neutral pH in compound parabolic collectors with 20 mg L−1 of Fe2+ and 50 mg L−1 of H2O2 in different matrices [saline solution (0.9% NaCl), saline solution with resorcinol and a simulated secondary effluent from a municipal wastewater treatment plant (SEWWTP)]. The effects of mechanical stress, acidic pH, solar light, solar light/H2O2 and Fenton reaction were determined. Sunlight led to a 2-log bacterial decrease while H2O2 (50 mg L−1) with solar light decreased E. faecalis concentration from 106 to 102 CFU mL−1 and 1-log for Fenton reaction after 100 min of treatment. The chemical composition of water matrix was shown to have a marked influence on E. faecalis inactivation by solar photo-Fenton. The detection limit was reached within 55 min in the saline solution. The presence of resorcinol (Dissolved Organic Carbon: 10 mg L−1) reduced the treatment time by 10 min; whilst a 15 min reduction was observed in SEWWTP and the final pH returned to neutral. E. faecalis inactivation results were satisfactorily fitted to a modified version of the classical Chick–Watson model. The kinetic constants were 0.193 ± 0.005 min−1 for saline solution, 0.294 ± 0.016 min−1 for saline solution with resorcinol, and 0.330 ± 0.019 min−1 for SEWWTP.