Abstract: Paracetamol has been reported to chelate with iron. It was found that no in vitro reaction between ferrous ion and paracetamol. Other studies found that there is an aerobic (in the gastrointestinal tract) oxidation of ferrous ion to ferric ion caused in iron-paracetamol in vivo reactions. The objective of this study was to determine if iron interacts with paracetamol and reduces paracetamol absorption. A randomized, double-blind, cross-over study design was used to assess the in vivo interaction of paracetamol and ferrous ion. Paracetamol (1.0 g) was co-ignested alone or with (300 mg) ferrous sulphate by ten healthy male volunteers, using saliva drug levels as a parameter. Concomitant administration of ferrous sulphate and paracetamol, decreased AUC8 from 42.88±3.8-34.25±2.8 μg h mL-1 (p = 0.04) and Cmax from 18.75±1.9 to 15.9±1.7 μg mL-1 (p = 0.11), while no change in tmax (p = 0.5) was originated. A significant difference was found in the paracetamol pharmacokinetic parameter oral clearance (Cl/F) (p = 0.02) and slightly increased in volume of distribution (Vd/F) (p = 0.10). Co-administration of iron and paracetamol results in decreased paracetamol absorption due to an interaction between iron and paracetamol.