Substituents that are conjugated with the site of proton gain or loss, and even substituents that are electronegative but not conjugating, can have significant effects on pKa values. Phenol has pKa 10 but phenols with anions stabilized by extra conjugation can have much lower pKas.

One nitro group, as in p-nitrophenol, lowers the pKa to 7.14, nearly a thousand-fold increase in acidity. This is because the negative charge on oxygen is delocalized into the very electron withdrawing nitro group. By contrast 4-chlorophenol, with only inductive withdrawal in the C–Cl bond, has pKa 9.38, hardly different from phenol itself.

Inductive effects of nearby electronegative atoms can also have marked effects on the pKa of acids. Adding fluorines to acetic acid reduces the pKa from about 5 by smallish steps. Trifluoroacetic acid (TFA) is a very strong acid indeed, and is commonly used as a convenient strong acid in organic reactions. Inductive effects occur by polarization of σ bonds when the atom at one end is more electronegative than at the other. Fluorine is much more electro-negative than carbon (indeed, F is the most electronegative element of all) so each σ bond is very polarized, making the carbon atom more electropositive and stabilizing the carboxylate anion.