Density functional theory (DFT) calculations were devised to get insight into Lewis acidic catalysis by POMs, especially on the intriguing activation of complexed water molecules that was observed in some experimental cases. Computationally, it appears that deprotonation is feasible with [alpha(1)-Hf(H2O)P2W17O61](6-), but not with [alpha(1)-Yb(H2O)P2W17O61](7-). This reflects the difference of the electronic structures (diamagnetic for hafnium POM, paramagnetic for ytterbium POM). From a mechanistical point of view, indirect Bronsted catalysis cannot be excluded in the hafnium case, especially for Mannich reactions. But our calculations show that catalysis by [alpha(1)-Yb(H2O)P2W17O61](7-) (and presumably all the lanthanide series) proceeds through direct complexation of the substrates to the POM.