Oxidative damage to RNA has been linked to change or loss of RNA function and development of many human age-related diseases. However, knowledge on the nature of RNA oxidative damage is relatively limited. In this study, oxidative damage to RNA is investigated under anaerobic and aerobic conditions by exploring the properties and reactions of 5-hydroxyl-2'-uridin-6-yl and its peroxyl diastereoisomers in the RNA strand, respectively. Selective addition of OH to the nucleic base from the 5'-end is studied at the molecular level for the first time, explaining the large number of the 5S-isomer available for further reactions. Our results provide clear evidence that the efficiency of C2'-H2' bond activation in the peroxyl isomers is lower than in the carbon radical species. An exception is observed for the isomer cis-(5S,6R)-A1, whose internucleotidyl H2'-abstraction barrier is far smaller than that in the corresponding C6-yl radical. However, analysis of the equilibrium species distribution reveals that the amount of cis-(5S,6R)Al is very small among the peroxyl diastereoisomers, and hence the resulting products from direct strand scission should be a less important component in RNA oxidative damage. The species with maximum distribution is the cis-(5S,6R)-B1 isomer, which is derived from cis-(5S,6R)-A1 and has a moderate intranucleotidyl H2'-abstraction barrier. More importantly, the reaction is mildly exothermic. These results show that the main fraction of the intranucleotidyl H2'-abstraction intermediates can be formed from the cis-(5S,6R)-B1 isomer. The absolute reduction potentials, the hydrogen atom binding energies, and the key structural parameters of the C6-peroxyl species are used to understand the diverse reactivity of the cis-(5S,6R) diastereoisomers toward the C2'-H2' bonds activation. The present study shows that in addition to the selectivity of the OH radical addition, there- is a strong correlation between the conformation of the modified uracil base and its reactivity in RNA oxidative damage.