For a complete engagement of virus-membrane fusion process, the viral and target membranes must merge, often observed via lipid mixing between both membranes. In Figure (top), the CHn stretching region shows the strongest peak at 2964 cm -1 , due to CH3 stretches of the HA fusion peptide, which dominate over potential viral or tBLM lipid signals (as indicated below the SEIRA spectra). To separate the spectral contributions due to virus and tBLM, we made use of the vibrational isotope effect and constructed the tBLM using deuterated POPC-d82. In this way, the tBLM lipids show CDn stretches at 2250 -2050 cm -1 , while CHn absorptions of the viral proteins and lipids remain at 3000 -2800 cm -1 . Repeating the pH-induced experiment, we obtain direct indications for lipid mixing. Accordingly, we observe the same positive HA amide and negative lipid C=O stretch signals as the virus engaged in the fusion processes (Figure bottom). In addition, the CHn stretching region (3000 -2800 cm -1 ) now shows a clear picture of positive lipid bands with a dominating CH2 peak at 2930 cm -1 due to viral lipids; at the same time, we detect a negative CDn stetching region (2250 -2050 cm -1 ) due to POPC-d82 lipids of the tBLM. This combination of positive CHn and negative CDn signals directly points towards an exchange of viral and deuterated lipids between both membranes. The opposite intensities also explain why the CHn region in Figure (top) showed a dominating spectrum of HA fusion peptide CHn stretches: in the absence of isotopeedited lipids, SEIRA signals due to lipids of virus and tBLM have cancelled out.