AbstractMonitoring the interaction of biomolecules is important, and the use of energy transfer is a principal technique in elucidating nanoscale interactions. Lanthanide compounds are promising luminescent probes for biological samples as their emission is longer‐lived than any native autofluorescence. Polyoxometalates (POMs) are interesting structural motifs to incorporate lanthanides, offering low toxicity and a size pertinent for biological applications. Here, we employ iso‐structured POMs containing either terbium or europium and assess their interaction with serum albumin by sensitisation of a fluorescent tag on the protein via LRET (luminescence resonance energy transfer) by exciting the lanthanide. Time‐resolved measurements showed energy transfer with an efficiency of over 90 % for the POM–protein systems. The Tb–POM results were relatively straightforward, while those with the iso‐structured Eu–POM were complicated by the effect of protein shielding from the aqueous environment.