Effect of ferric ions at concentrations typically found in natural waters (0.05 to 1.06 mg L −1 ) and low H 2 O 2 concentrations (between 0.5 and 17.9 mg L −1 ) on simulated sunlight-induced (300 W m −2 ) photo-Fenton degradation at initial neutral pH (7.0) of amoxicillin and diuron in Milli-Q water was studied using an rotatable central composite experimental design 2 2 with a central and two axial points. H 2 O 2 concentration was the parameter playing the key role on the degradation of both pollutants. Despite that initial pH was 7.0 in Milli-Q water, this latter decreased rapidly in the first minutes, reaching values of 3.5 and 5.0 for diuron and amoxicillin respectively after 15 min of simulated sunlight irradiation. In contrast, in presence of bicarbonate/carbonate (HCO 3), fluoride (F − ), and humic acids (HAs) at concentrations found often in surface and well waters with ferric ion and H 2 O 2 concentrations of 0.3 and 9.7 and 15.2 mg L −1 respectively, both pollutants exhibited a strong degradation keeping the circumneutral pH. Amoxicillin and diuron degradation byproducts found by HPLC/MS were compatible with HO • and/or CO 3 -• radical attack. Several photo-induced processes such as photo-Fenton (by dissolved ferric-HA complexes), heterogeneous photocatalysis (by colloidal iron), UV-B H 2 O 2 photolysis, irradiated-dissolved organic matter, and their reactions with pollutants would be the main oxidative route responsible of degradations. These findings demonstrated that it could be possible using iron concentrations often found in natural waters to oxidize via photo-Fenton processes among other events, organic pollutants at natural pH conditions.Keywords Circumneutral photo-Fenton . Diuron . Amoxicillin . H 2 O 2 photolysis . Water detoxification . Low iron amounts * Paula Osorio-Vargas