The acid–base chemistry of luteolin, a flavonoid with important pharmacological and dyeing properties, and of the related methyl ether derivatives have been investigated by DFT and MP2 methods, testing different computational setups. We calculate the p K a ’s of all the possible deprotonation sites, for which no experimental assignment could be achieved. The calculated p K a ’s deliver a different acidity order for the two most acidic deprotonation sites between luteolin and its methyl ether derivatives, due to intramolecular hydrogen bonding in luteolin. A lowest p K a of 6.19 is computed for luteolin, in good agreement with available experimental data.