The flavodiiron proteins (FDP) are widespread among strict or facultative anaerobic prokaryotes, where they are involved in the response to nitrosative and/or oxidative stress. Unexpectedly, FDPs were fairly recently identified in a restricted group of microaerobic protozoa, including Giardia intestinalis, the causative agent of the human infectious disease giardiasis. The FDP from Giardia was expressed, purified and extensively characterized by X-ray crystallography, stopped-flow spectroscopy, respirometry and NO amperometry. Contrary to flavorubredoxin, the FDP from Escherichia coli, the enzyme from Giardia has high O₂-reductase activity (> 40 s^-1), but very low NO-reductase activity (~ 0.2 s^-1); O₂ reacts with the reduced protein quite rapidly (milliseconds) and with high affinity (K_M = 2 µM), producing H₂O. The 3D structure of the oxidized protein determined at 1.9 Å resolution shows remarkable similarities with prokaryotic FDPs. Consistent with HPLC analysis, the enzyme is a dimer of dimers with FMN and the non-heme di-iron site topologically close at the monomer-monomer interface. Unlike the FDP from Desulfovibrio gigas, the residue H90 is a ligand of the di-iron site, in contrast with the proposal that ligation of this histidine is crucial for a preferential specificity for NO. We propose that in Giardia intestinalis the primary function of FDP is to efficiently scavenge O₂, allowing this microaerobic parasite to survive in the human small intestine, thus promoting its pathogenicity.